Compositions and methods for treating sepsis

Abstract

The disclosure features compositions and methods that are useful for treatment of a subject having sepsis. In particular, methods for treating sepsis involving the administration of CD11c agonists are disclosed herein.

Description

[0001]Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 COMPOSITIONS AND METHODS FOR TREATING SEPSIS CROSS REFERENCE TO RELATED APPLICATIONS The present application claims priority to and the benefit of U.S. App. No.63 / 653,522, filed May 30, 2024, the contents of which is hereby incorporated by reference in its entirety. STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH This invention was made with government support under grant No. GM148392 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND OF THE DISCLOSURE Sepsis is a serious condition in which the body responds improperly to an infection and remains a difficult disease to treat. For example, in the U.S, its mortality ranges from 20 to 30% in both adults and children with an annual cost of $24 billion, accounting for nearly one-fifth of the total aggregate costs in all hospitalizations. The mortality is much higher in developing countries. To date sepsis management has been largely supportive, and no effective therapeutics exist. With the emergence of many antibiotics-resistant microbes, therapeutics for sepsis represent an urgent unmet medical need. SUMMARY OF THE DISCLOSURE As described below, the present disclosure features compositions and methods for treating sepsis in a subject. In an aspect, the present disclosure provides a method of inducing neutrophil maturation. The method involves contacting a neutrophil with a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, thereby inducing neutrophil maturation. In another aspect, the present disclosure provides a method of inducing neutrophil mobilization and maturation in a subject. The method involves administering to the subject granulocyte colony-stimulating factor (G-CSF) and a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, where the CD11c agonist and the G-CSF are administered sequentially or concurrently, thereby inducing neutrophil mobilization and maturation in the subject. In another aspect, the present disclosure provides a method of enhancing an immune response in a subject. The method involves administering to the subject a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a- heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, thereby enhancing an immune response in the subject In another aspect, the present disclosure provides a method of treating sepsis in a subject in need thereof. The method involves administering to the subject a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, thereby, thereby treating the sepsis. In another aspect the present disclosure provides a combination therapy including a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy- 1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene- 4a-carboxylic acid; Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, and a G-CSF. In another aspect, the present disclosure provides a pharmaceutical composition including a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy- 1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene- 4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, a G-CSF, and a pharmaceutically acceptable excipient. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 In another aspect the present disclosure provides a kit including a CD11c agonist, where the agonist is (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a- heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213-didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; or UNC2250, or a pharmaceutical composition thereof, and instructions for using the CD11c agonist or the pharmaceutical composition in the method of any of the above aspects, or embodiments thereof. In any of the above aspects, or embodiments thereof, the neutrophil is in vitro or in vivo. In any of the above aspects, or embodiments thereof, the G-CSF is administered prior to the CD11c agonist. In any of the above aspects, or embodiments thereof, the subject has a bacterial infection and / or sepsis. In any of the above aspects, or embodiments thereof, the method further involves administering a granulocyte colony-stimulating factor (G-CSF) to the subject. In any of the above aspects, or embodiments thereof, the CD11c agonist and the G-CSF are formulated together or separately. Other features and advantages of the disclosure will be apparent from the detailed description, and from the claims. Definitions Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this disclosure belongs. The Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 following references provide one of skill with a general definition of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise. By "agent" is meant any small molecule chemical compound, nucleic acid molecule, or polypeptide, or fragments thereof. In embodiments, the agent is a CD11c agonist or antagonist. By “agonist” is meant an agent that binds to a receptor and produces a response. A CD11c agonist upregulates CD11c activity and / or expression by at least about 10%, 20%, 30%, 50%, 75%, or more. By "alteration" is meant a change (increase or decrease) in a clinical indication, or in the expression levels or activity of a gene or polypeptide as detected by standard art known methods, such as those described herein. As used herein, an alteration includes a 10% change in expression levels, a 25% change, a 40% change, and even a 50% or greater change in expression levels. By “ameliorate” is meant decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a disease. In embodiments, the disease is sepsis. By "analog" is meant a molecule that is not identical, but has analogous functional or structural features. For example, a polypeptide analog retains the biological activity of a corresponding naturally-occurring polypeptide, while having certain biochemical modifications that enhance the analog's function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog's protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding. An analog may include an unnatural amino acid. By “antagonist” is meant an agent binds to a receptor and stops the receptor from producing a response. A CD11c antagonist inhibits CD11c activity and / or expression by at least about 10%, 20%, 30%, 50%, 75%, or more. “Biological sample” as used herein means a biological material isolated from a subject. Exemplary biological samples include any tissue, cell, fluid, or other material obtained from or derived from the subject. In some embodiments, the subject is human. The biological sample may contain any biological material suitable for detecting the desired analytes (e.g., a mosaic chromosomal alteration), and may comprise cellular and / or non-cellular material obtained from the subject. The biological sample preferably comprises DNA. In particular embodiments, the Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 biological sample is blood. Biological samples include tissue samples (e.g., cell samples, biopsy samples). Biological samples also include bodily fluids, including, but not limited to, cerebrospinal fluid, blood, lymph, blood serum, plasma, saliva, and urine. In some embodiments, the biological sample comprises blood, skin, sputum, gargles, bronchial washings, urine, semen, feces, cerebrospinal fluid, biopsies, or dried blood spots. A “biomarker” or “marker” as used herein generally refers to a protein, nucleic acid molecule, clinical indicator, or other analyte that is associated with a disease. In one embodiment, a marker of sepsis is differentially present in a biological sample obtained from a subject having or at risk of developing sepsis relative to a reference. In another embodiment, a marker can be used to characterize the stage of immune and / or inflammatory dysfunction in a subject diagnosed as having sepsis, septic shock, systemic inflammatory response syndrome, compensatory anti-inflammatory response syndrome or related disorders. A marker is differentially present if the mean or median level of the marker present in the sample is statistically different from the level present in a reference. A reference level may be, for example, the level present in a sample obtained from a healthy control subject the level obtained from the subject at an earlier timepoint, i.e., prior to treatment, or the level obtained from a subject at a defined stage of septic illness. Common tests for statistical significance include, among others, t-test, ANOVA, Kruskal-Wallis, Wilcoxon, Mann-Whitney and odds ratio. Biomarkers, alone or in combination, provide measures of relative likelihood that a subject belongs to a phenotypic status of interest. The differential presence of a marker of the invention in a subject sample can be useful in characterizing the immune dysfunction present in a subject identified as having or at risk of developing sepsis, for determining the prognosis of the subject, for evaluating therapeutic efficacy, or for selecting a treatment regimen. By “CD11c polypeptide” or “CD11 antigen-like family member C polypeptide” is meant a polypeptide having at least about 85% amino acid sequence identity to NCBI Accession Nos. NP_000878.2 or NP_001273304.1, or a fragment thereof having integrin beta 2 chain (ITGB2) binding activity. CD11c may also be known as integrin subunit alpha X, integrin alpha X, or ITGAX. Exemplary CD11c amino acid sequences are provided below: >NP_000878.2 integrin alpha-X isoform 2 precursor [Homo sapiens] MTRTRAALLLFTALATSLGFNLDTEELTAFRVDSAGFGDSVVQYANSWVVVGAPQKITAANQTGGLYQCG YSTGACEPIGLQVPPEAVNMSLGLSLASTTSPSQLLACGPTVHHECGRNMYLTGLCFLLGPTQLTQRLPV SRQECPRQEQDIVFLIDGSGSISSRNFATMMNFVRAVISQFQRPSTQFSLMQFSNKFQTHFTFEEFRRSS NPLSLLASVHQLQGFTYTATAIQNVVHRLFHASYGARRDAAKILIVITDGKKEGDSLDYKDVIPMADAAG IIRYAIGVGLAFQNRNSWKELNDIASKPSQEHIFKVEDFDALKDIQNQLKEKIFAIEGTETTSSSSFELE MAQEGFSAVFTPDGPVLGAVGSFTWSGGAFLYPPNMSPTFINMSQENVDMRDSYLGYSTELALWKGVQSL Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 VLGAPRYQHTGKAVIFTQVSRQWRMKAEVTGTQIGSYFGASLCSVDVDSDGSTDLVLIGAPHYYEQTRGG QVSVCPLPRGWRRWWCDAVLYGEQGHPWGRFGAALTVLGDVNGDKLTDVVIGAPGEEENRGAVYLFHGVL GPSISPSHSQRIAGSQLSSRLQYFGQALSGGQDLTQDGLVDLAVGARGQVLLLRTRPVLWVGVSMQFIPA EIPRSAFECREQVVSEQTLVQSNICLYIDKRSKNLLGSRDLQSSVTLDLALDPGRLSPRATFQETKNRSL SRVRVLGLKAHCENFNLLLPSCVEDSVTPITLRLNFTLVGKPLLAFRNLRPMLAADAQRYFTASLPFEKN CGADHICQDNLGISFSFPGLKSLLVGSNLELNAEVMVWNDGEDSYGTTITFSHPAGLSYRYVAEGQKQGQ LRSLHLTCDSAPVGSQGTWSTSCRINHLIFRGGAQITFLATFDVSPKAVLGDRLLLTANVSSENNTPRTS KTTFQLELPVKYAVYTVVSSHEQFTKYLNFSESEEKESHVAMHRYQVNNLGQRDLPVSINFWVPVELNQE AVWMDVEVSHPQNPSLRCSSEKIAPPASDFLAHIQKNPVLDCSIAGCLRFRCDVPSFSVQEELDFTLKGN LSFGWVRQILQKKVSVVSVAEITFDTSVYSQLPGQEAFMRAQTTTVLEKYKVHNPTPLIVGSSIGGLLLL ALITAVLYKVGFFKRQYKEMMEEANGQIAPENGTQTPSPPSEK >NP_001273304.1 integrin alpha-X isoform 1 precursor [Homo sapiens] MTRTRAALLLFTALATSLGFNLDTEELTAFRVDSAGFGDSVVQYANSWVVVGAPQKITAANQTGGLYQCG YSTGACEPIGLQVPPEAVNMSLGLSLASTTSPSQLLACGPTVHHECGRNMYLTGLCFLLGPTQLTQRLPV SRQECPRQEQDIVFLIDGSGSISSRNFATMMNFVRAVISQFQRPSTQFSLMQFSNKFQTHFTFEEFRRSS NPLSLLASVHQLQGFTYTATAIQNVVHRLFHASYGARRDAAKILIVITDGKKEGDSLDYKDVIPMADAAG IIRYAIGVGLAFQNRNSWKELNDIASKPSQEHIFKVEDFDALKDIQNQLKEKIFAIEGTETTSSSSFELE MAQEGFSAVFTPDGPVLGAVGSFTWSGGAFLYPPNMSPTFINMSQENVDMRDSYLGYSTELALWKGVQSL VLGAPRYQHTGKAVIFTQVSRQWRMKAEVTGTQIGSYFGASLCSVDVDSDGSTDLVLIGAPHYYEQTRGG QVSVCPLPRGWRRWWCDAVLYGEQGHPWGRFGAALTVLGDVNGDKLTDVVIGAPGEEENRGAVYLFHGVL GPSISPSHSQRIAGSQLSSRLQYFGQALSGGQDLTQDGLVDLAVGARGQVLLLRTRPVLWVGVSMQFIPA EIPRSAFECREQVVSEQTLVQSNICLYIDKRSKNLLGSRDLQSSVTLDLALDPGRLSPRATFQETKNRSL SRVRVLGLKAHCENFNLLLPSCVEDSVTPITLRLNFTLVGKPLLAFRNLRPMLAADAQRYFTASLPFEKN CGADHICQDNLGISFSFPGLKSLLVGSNLELNAEVMVWNDGEDSYGTTITFSHPAGLSYRYVAEGQKQGQ LRSLHLTCDSAPVGSQGTWSTSCRINHLIFRGGAQITFLATFDVSPKAVLGDRLLLTANVSSENNTPRTS KTTFQLELPVKYAVYTVVSSHEQFTKYLNFSESEEKESHVAMHRYQVNNLGQRDLPVSINFWVPVELNQE AVWMDVEVSHPQNPSLRCSSEKIAPPASDFLAHIQKNPVLDCSIAGCLRFRCDVPSFSVQEELDFTLKGN LSFGWVRQILQKKVSVVSVAEITFDTSVYSQLPGQEAFMRAQTTTVLEKYKVHNPTPLIVGSSIGGLLLL ALITAVLYKVGFFKRQYKEMMEEANGQIAPENGTQTPSPPTPHYPQDNV By “CD11c polynucleotide” or “CD11 antigen-like family member C polynucleotide” is meant a nucleic acid molecule encoding a CD11c polypeptide. Exemplary CD11c polynucleotide sequences may be found below: >NM_000887.5 Homo sapiens integrin subunit alpha X (ITGAX), transcript variant 2, mRNA ACTTGCTTCCTCAGTACCTTGGTCCAGCTCTTCCTGCAACGGCCCAGGAGCTCAGAGCTCCACATCTGAC CTTCTAGTCATGACCAGGACCAGGGCAGCACTCCTCCTGTTCACAGCCTTAGCAACTTCTCTAGGTTTCA ACTTGGACACAGAGGAGCTGACAGCCTTCCGTGTGGACAGCGCTGGGTTTGGAGACAGCGTGGTCCAGTA TGCCAACTCCTGGGTGGTGGTTGGAGCCCCCCAAAAGATAACAGCTGCCAACCAAACGGGTGGCCTCTAC CAGTGTGGCTACAGCACTGGTGCCTGTGAGCCCATCGGCCTGCAGGTGCCCCCGGAGGCCGTGAACATGT CCCTGGGCCTGTCCCTGGCGTCTACCACCAGCCCTTCCCAGCTGCTGGCCTGCGGCCCCACCGTGCACCA CGAGTGCGGGAGGAACATGTACCTCACCGGACTCTGCTTCCTCCTGGGCCCCACCCAGCTCACCCAGAGG Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 CTCCCGGTGTCCAGGCAGGAGTGCCCAAGACAGGAGCAGGACATTGTGTTCCTGATCGATGGCTCAGGCA GCATCTCCTCCCGCAACTTTGCCACGATGATGAACTTCGTGAGAGCTGTGATAAGCCAGTTCCAGAGACC CAGCACCCAGTTTTCCCTGATGCAGTTCTCCAACAAATTCCAAACACACTTCACTTTCGAGGAATTCAGG CGCAGCTCAAACCCCCTCAGCCTGTTGGCTTCTGTTCACCAGCTGCAAGGGTTTACATACACGGCCACCG CCATCCAAAATGTCGTGCACCGATTGTTCCATGCCTCATATGGGGCCCGTAGGGATGCCGCCAAAATTCT CATTGTCATCACTGATGGGAAGAAAGAAGGCGACAGCCTGGATTATAAGGATGTCATCCCCATGGCTGAT GCAGCAGGCATCATCCGCTATGCAATTGGGGTTGGATTAGCTTTTCAAAACAGAAATTCTTGGAAAGAAT TAAATGACATTGCATCGAAGCCCTCCCAGGAACACATATTTAAAGTGGAGGACTTTGATGCTCTGAAAGA TATTCAAAACCAACTGAAGGAGAAGATCTTTGCCATTGAGGGTACGGAGACCACAAGCAGTAGCTCCTTC GAATTGGAGATGGCACAGGAGGGCTTCAGCGCTGTGTTCACACCTGATGGCCCCGTTCTGGGGGCTGTGG GGAGCTTCACCTGGTCTGGAGGTGCCTTCCTGTACCCCCCAAATATGAGCCCTACCTTCATCAACATGTC TCAGGAGAATGTGGACATGAGGGACTCTTACCTGGGTTACTCCACCGAGCTGGCCCTCTGGAAAGGGGTG CAGAGCCTGGTCCTGGGGGCCCCCCGCTACCAGCACACCGGGAAGGCTGTCATCTTCACCCAGGTGTCCA GGCAATGGAGGATGAAGGCCGAAGTCACGGGGACTCAGATCGGCTCCTACTTCGGGGCCTCCCTCTGCTC CGTGGACGTAGACAGCGACGGCAGCACCGACCTGGTCCTCATCGGGGCCCCCCATTACTACGAGCAGACC CGAGGGGGCCAGGTGTCTGTGTGTCCCTTGCCCAGGGGGTGGAGAAGGTGGTGGTGTGATGCTGTTCTCT ACGGGGAGCAGGGCCACCCCTGGGGTCGCTTTGGGGCGGCTCTGACAGTGCTGGGGGATGTGAATGGGGA CAAGCTGACAGACGTGGTCATCGGGGCCCCAGGAGAGGAGGAGAACCGGGGTGCTGTCTACCTGTTTCAC GGAGTCTTGGGACCCAGCATCAGCCCCTCCCACAGCCAGCGGATCGCGGGCTCCCAGCTCTCCTCCAGGC TGCAGTATTTTGGGCAGGCACTGAGCGGGGGTCAAGACCTCACCCAGGATGGACTGGTGGACCTGGCTGT GGGGGCCCGGGGCCAGGTGCTCCTGCTCAGGACCAGACCTGTGCTCTGGGTGGGGGTGAGCATGCAGTTC ATACCTGCCGAGATCCCCAGGTCTGCGTTTGAGTGTCGGGAGCAGGTGGTCTCTGAGCAGACCCTGGTAC AGTCCAACATCTGCCTTTACATTGACAAACGTTCTAAGAACCTGCTTGGGAGCCGTGACCTCCAAAGCTC TGTGACCTTGGACCTGGCCCTCGACCCTGGCCGCCTGAGTCCCCGTGCCACCTTCCAGGAAACAAAGAAC CGGAGTCTGAGCCGAGTCCGAGTCCTCGGGCTGAAGGCACACTGTGAAAACTTCAACCTGCTGCTCCCGA GCTGCGTGGAGGACTCTGTGACCCCCATTACCTTGCGTCTGAACTTCACGCTGGTGGGCAAGCCCCTCCT TGCCTTCAGAAACCTGCGGCCTATGCTGGCCGCCGATGCTCAGAGATACTTCACGGCCTCCCTACCCTTT GAGAAGAACTGTGGAGCCGACCATATCTGCCAGGACAATCTCGGCATCTCCTTCAGCTTCCCAGGCTTGA AGTCCCTGCTGGTGGGGAGTAACCTGGAGCTGAACGCAGAAGTGATGGTGTGGAATGACGGGGAAGACTC CTACGGAACCACCATCACCTTCTCCCACCCCGCAGGACTGTCCTACCGCTACGTGGCAGAGGGCCAGAAA CAAGGGCAGCTGCGTTCCCTGCACCTGACATGTGACAGCGCCCCAGTTGGGAGCCAGGGCACCTGGAGCA CCAGCTGCAGAATCAACCACCTCATCTTCCGTGGCGGCGCCCAGATCACCTTCTTGGCTACCTTTGACGT CTCCCCCAAGGCTGTCCTGGGAGACCGGCTGCTTCTGACAGCCAATGTGAGCAGTGAGAACAACACTCCC AGGACCAGCAAGACCACCTTCCAGCTGGAGCTCCCGGTGAAGTATGCTGTCTACACTGTGGTTAGCAGCC ACGAACAATTCACCAAATACCTCAACTTCTCAGAGTCTGAGGAGAAGGAAAGCCATGTGGCCATGCACAG ATACCAGGTCAATAACCTGGGACAGAGGGACCTGCCTGTCAGCATCAACTTCTGGGTGCCTGTGGAGCTG AACCAGGAGGCTGTGTGGATGGATGTGGAGGTCTCCCACCCCCAGAACCCATCCCTTCGGTGCTCCTCAG AGAAAATCGCACCCCCAGCATCTGACTTCCTGGCGCACATTCAGAAGAATCCCGTGCTGGACTGCTCCAT TGCTGGCTGCCTGCGGTTCCGCTGTGACGTCCCCTCCTTCAGCGTCCAGGAGGAGCTGGATTTCACCCTG AAGGGCAACCTCAGCTTTGGCTGGGTCCGCCAGATATTGCAGAAGAAGGTGTCGGTCGTGAGTGTGGCTG AAATTACGTTCGACACATCCGTGTACTCCCAGCTTCCAGGACAGGAGGCATTTATGAGAGCTCAGACGAC Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 AACGGTGCTGGAGAAGTACAAGGTCCACAACCCCACCCCCCTCATCGTAGGCAGCTCCATTGGGGGTCTG TTGCTGCTGGCACTCATCACAGCGGTACTGTACAAAGTTGGCTTCTTCAAGCGTCAGTACAAGGAAATGA TGGAGGAGGCAAATGGACAAATTGCCCCAGAAAACGGGACACAGACCCCCAGCCCGCCCAGTGAGAAATG ATCCCCTCTTTGCCTTGGACTTCTTCTCCCCCGCGAGTTTTCCCCACTTACTTACCCTCACCTGTCAGGC CTGACGGGGAGGAACCACTGCACCACCGAGAGAGGCTGGGATGGGCCTGCTTCCTGTCTTTGGGAGAAAA CGTCTTGCTTGGGAAGGGGCCTTTGTCTTGTCAAGGTTCCAACTGGAAACCCTTAGGACAGGGTCCCTGC TGTGTTCCCCAAAGGACTTGACTTGCAATTTCTACCTAGAAATACATGGACAATACCCCCAGGCCTCAGT CTCCCTTCTCCCATGAGGCACGAATGATCTTTCTTTCCTTTCTTTTTTTTTTTTTTTCTTTTCTTTTTTT TTTTTTTGAGACGGAGTCTCGCTCTGTCACCCAGGCTGGAGTGCAATGGCGTGATCTCGGCTCACTGCAA CCTCCGCCTCCCGGGTTCAAGTAATTCTGCTGTCTCAGCCTCCTGAGTAGCTGGGACTACAGGCACACGC CACCTCGCCCGGCCCGATCTTTCTAAAATACAGTTCTGAATATGCTGCTCATCCCCACCTGTCTTCAACA GCTCCCCATTACCCTCAGGACAATGTCTGAACTCTCCAGCTTCGCGTGAGAAGTCCCCTTCCATCCCAGA GGGTGGGCTTCAGGGCGCACAGCATGAGAGGCTCTGTGCCCCCATCACCCTCGTTTCCAGTGAATTAGTG TCATGTCAGCATCAGCTCAGGGCTTCATCGTGGGGCTCTCAGTTCCGATTTCCCAGGCTGAATTGGGAGT GAGATGCCTGCATGCTGGGTTCTGCACAGCTGGCCTCCCGCGTTGGGCAACATTGCTGGCTGGAAGGGAG GAGCGCCCTCTAGGGAGGGACATGGCCCCGGTGCGGCTGCAGCTCACCCAGCCCCAGGGGCAGAAGAGAC CCAACCACTTCTATTTTTTGAGGCTATGAATATAGTACCTGAAAAAATGCCAAGACATGATTATTTTTTT AAAAAGCGTACTTTAAATGTTTGTGTTAATAAATTAAAACATGCACAAAAAGATGCATCTACCGCTCTTG GGAAATATGTCAAAGGTCTAAAAATAAAAAAGCCTTCTGTGGA >NM_001286375.2 Homo sapiens integrin subunit alpha X (ITGAX), transcript variant 1, mRNA ACTTGCTTCCTCAGTACCTTGGTCCAGCTCTTCCTGCAACGGCCCAGGAGCTCAGAGCTCCACATCTGAC CTTCTAGTCATGACCAGGACCAGGGCAGCACTCCTCCTGTTCACAGCCTTAGCAACTTCTCTAGGTTTCA ACTTGGACACAGAGGAGCTGACAGCCTTCCGTGTGGACAGCGCTGGGTTTGGAGACAGCGTGGTCCAGTA TGCCAACTCCTGGGTGGTGGTTGGAGCCCCCCAAAAGATAACAGCTGCCAACCAAACGGGTGGCCTCTAC CAGTGTGGCTACAGCACTGGTGCCTGTGAGCCCATCGGCCTGCAGGTGCCCCCGGAGGCCGTGAACATGT CCCTGGGCCTGTCCCTGGCGTCTACCACCAGCCCTTCCCAGCTGCTGGCCTGCGGCCCCACCGTGCACCA CGAGTGCGGGAGGAACATGTACCTCACCGGACTCTGCTTCCTCCTGGGCCCCACCCAGCTCACCCAGAGG CTCCCGGTGTCCAGGCAGGAGTGCCCAAGACAGGAGCAGGACATTGTGTTCCTGATCGATGGCTCAGGCA GCATCTCCTCCCGCAACTTTGCCACGATGATGAACTTCGTGAGAGCTGTGATAAGCCAGTTCCAGAGACC CAGCACCCAGTTTTCCCTGATGCAGTTCTCCAACAAATTCCAAACACACTTCACTTTCGAGGAATTCAGG CGCAGCTCAAACCCCCTCAGCCTGTTGGCTTCTGTTCACCAGCTGCAAGGGTTTACATACACGGCCACCG CCATCCAAAATGTCGTGCACCGATTGTTCCATGCCTCATATGGGGCCCGTAGGGATGCCGCCAAAATTCT CATTGTCATCACTGATGGGAAGAAAGAAGGCGACAGCCTGGATTATAAGGATGTCATCCCCATGGCTGAT GCAGCAGGCATCATCCGCTATGCAATTGGGGTTGGATTAGCTTTTCAAAACAGAAATTCTTGGAAAGAAT TAAATGACATTGCATCGAAGCCCTCCCAGGAACACATATTTAAAGTGGAGGACTTTGATGCTCTGAAAGA TATTCAAAACCAACTGAAGGAGAAGATCTTTGCCATTGAGGGTACGGAGACCACAAGCAGTAGCTCCTTC GAATTGGAGATGGCACAGGAGGGCTTCAGCGCTGTGTTCACACCTGATGGCCCCGTTCTGGGGGCTGTGG GGAGCTTCACCTGGTCTGGAGGTGCCTTCCTGTACCCCCCAAATATGAGCCCTACCTTCATCAACATGTC TCAGGAGAATGTGGACATGAGGGACTCTTACCTGGGTTACTCCACCGAGCTGGCCCTCTGGAAAGGGGTG CAGAGCCTGGTCCTGGGGGCCCCCCGCTACCAGCACACCGGGAAGGCTGTCATCTTCACCCAGGTGTCCA Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 GGCAATGGAGGATGAAGGCCGAAGTCACGGGGACTCAGATCGGCTCCTACTTCGGGGCCTCCCTCTGCTC CGTGGACGTAGACAGCGACGGCAGCACCGACCTGGTCCTCATCGGGGCCCCCCATTACTACGAGCAGACC CGAGGGGGCCAGGTGTCTGTGTGTCCCTTGCCCAGGGGGTGGAGAAGGTGGTGGTGTGATGCTGTTCTCT ACGGGGAGCAGGGCCACCCCTGGGGTCGCTTTGGGGCGGCTCTGACAGTGCTGGGGGATGTGAATGGGGA CAAGCTGACAGACGTGGTCATCGGGGCCCCAGGAGAGGAGGAGAACCGGGGTGCTGTCTACCTGTTTCAC GGAGTCTTGGGACCCAGCATCAGCCCCTCCCACAGCCAGCGGATCGCGGGCTCCCAGCTCTCCTCCAGGC TGCAGTATTTTGGGCAGGCACTGAGCGGGGGTCAAGACCTCACCCAGGATGGACTGGTGGACCTGGCTGT GGGGGCCCGGGGCCAGGTGCTCCTGCTCAGGACCAGACCTGTGCTCTGGGTGGGGGTGAGCATGCAGTTC ATACCTGCCGAGATCCCCAGGTCTGCGTTTGAGTGTCGGGAGCAGGTGGTCTCTGAGCAGACCCTGGTAC AGTCCAACATCTGCCTTTACATTGACAAACGTTCTAAGAACCTGCTTGGGAGCCGTGACCTCCAAAGCTC TGTGACCTTGGACCTGGCCCTCGACCCTGGCCGCCTGAGTCCCCGTGCCACCTTCCAGGAAACAAAGAAC CGGAGTCTGAGCCGAGTCCGAGTCCTCGGGCTGAAGGCACACTGTGAAAACTTCAACCTGCTGCTCCCGA GCTGCGTGGAGGACTCTGTGACCCCCATTACCTTGCGTCTGAACTTCACGCTGGTGGGCAAGCCCCTCCT TGCCTTCAGAAACCTGCGGCCTATGCTGGCCGCCGATGCTCAGAGATACTTCACGGCCTCCCTACCCTTT GAGAAGAACTGTGGAGCCGACCATATCTGCCAGGACAATCTCGGCATCTCCTTCAGCTTCCCAGGCTTGA AGTCCCTGCTGGTGGGGAGTAACCTGGAGCTGAACGCAGAAGTGATGGTGTGGAATGACGGGGAAGACTC CTACGGAACCACCATCACCTTCTCCCACCCCGCAGGACTGTCCTACCGCTACGTGGCAGAGGGCCAGAAA CAAGGGCAGCTGCGTTCCCTGCACCTGACATGTGACAGCGCCCCAGTTGGGAGCCAGGGCACCTGGAGCA CCAGCTGCAGAATCAACCACCTCATCTTCCGTGGCGGCGCCCAGATCACCTTCTTGGCTACCTTTGACGT CTCCCCCAAGGCTGTCCTGGGAGACCGGCTGCTTCTGACAGCCAATGTGAGCAGTGAGAACAACACTCCC AGGACCAGCAAGACCACCTTCCAGCTGGAGCTCCCGGTGAAGTATGCTGTCTACACTGTGGTTAGCAGCC ACGAACAATTCACCAAATACCTCAACTTCTCAGAGTCTGAGGAGAAGGAAAGCCATGTGGCCATGCACAG ATACCAGGTCAATAACCTGGGACAGAGGGACCTGCCTGTCAGCATCAACTTCTGGGTGCCTGTGGAGCTG AACCAGGAGGCTGTGTGGATGGATGTGGAGGTCTCCCACCCCCAGAACCCATCCCTTCGGTGCTCCTCAG AGAAAATCGCACCCCCAGCATCTGACTTCCTGGCGCACATTCAGAAGAATCCCGTGCTGGACTGCTCCAT TGCTGGCTGCCTGCGGTTCCGCTGTGACGTCCCCTCCTTCAGCGTCCAGGAGGAGCTGGATTTCACCCTG AAGGGCAACCTCAGCTTTGGCTGGGTCCGCCAGATATTGCAGAAGAAGGTGTCGGTCGTGAGTGTGGCTG AAATTACGTTCGACACATCCGTGTACTCCCAGCTTCCAGGACAGGAGGCATTTATGAGAGCTCAGACGAC AACGGTGCTGGAGAAGTACAAGGTCCACAACCCCACCCCCCTCATCGTAGGCAGCTCCATTGGGGGTCTG TTGCTGCTGGCACTCATCACAGCGGTACTGTACAAAGTTGGCTTCTTCAAGCGTCAGTACAAGGAAATGA TGGAGGAGGCAAATGGACAAATTGCCCCAGAAAACGGGACACAGACCCCCAGCCCGCCCACTCCCCATTA CCCTCAGGACAATGTCTGAACTCTCCAGCTTCGCGTGAGAAGTCCCCTTCCATCCCAGAGGGTGGGCTTC AGGGCGCACAGCATGAGAGGCTCTGTGCCCCCATCACCCTCGTTTCCAGTGAATTAGTGTCATGTCAGCA TCAGCTCAGGGCTTCATCGTGGGGCTCTCAGTTCCGATTTCCCAGGCTGAATTGGGAGTGAGATGCCTGC ATGCTGGGTTCTGCACAGCTGGCCTCCCGCGTTGGGCAACATTGCTGGCTGGAAGGGAGGAGCGCCCTCT AGGGAGGGACATGGCCCCGGTGCGGCTGCAGCTCACCCAGCCCCAGGGGCAGAAGAGACCCAACCACTTC TATTTTTTGAGGCTATGAATATAGTACCTGAAAAAATGCCAAGACATGATTATTTTTTTAAAAAGCGTAC TTTAAATGTTTGTGTTAATAAATTAAAACATGCACAAAAAGATGCATCTACCGCTCTTGGGAAATATGTC AAAGGTCTAAAAATAAAAAAGCCTTCTGTGGA In this disclosure, "comprises," "comprising," "containing", and "having" and the like can have the meaning ascribed to them in U.S. Patent law and can mean " includes," "including," and Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 the like; "consisting essentially of" or "consists essentially" likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments. Any embodiments specified as “comprising” a particular component(s) or element(s) are also contemplated as “consisting of” or “consisting essentially of” the particular component(s) or element(s) in some embodiments. By “decreases” is meant a reduction by at least about 5% relative to a reference level. A decrease may be by 5%, 10%, 15%, 20%, 25% or 50%, or even by as much as 75%, 85%, 95% or more and any intervening percentages. “Detect” refers to identifying the presence, absence or amount of the analyte to be detected. By “disease” is meant any condition or disorder that damages or interferes with the normal function of a cell, tissue, or organ. In an embodiment, the disease is sepsis. The term “expression” or “expressed” as used herein in reference to a gene means the transcriptional and / or translational product of that gene. The level of expression of a DNA molecule in a cell may be determined on the basis of either the amount of corresponding mRNA that is present within the cell or the amount of protein encoded by that DNA produced by the cell (Sambrook et al., 1989 Molecular Cloning: A Laboratory Manual, 18.1-18.88). By "effective amount" is meant the amount of an agent required to ameliorate, reduce, or prevent the symptoms of a disease relative to an untreated patient. The effective amount of active compound(s) used to practice the present disclosure for therapeutic treatment of a disease varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such amount is referred to as an "effective" amount. By "fragment" is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. As used herein, “obtaining” as in “obtaining an agent” includes synthesizing, purchasing, or otherwise acquiring the agent. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 By “prevent,” “preventing,” “prevention,” “prophylactic treatment”, and the like is meant reducing the probability of developing a disorder, disease, or condition in a subject, who does not have, but is at risk of or susceptible to developing the disorder, disease, or condition. By “reduces” is meant a negative alteration of at least 1%, 5%, 10%, 25%, 50%, 75%, or 100%. By “reference” is meant a standard or control condition. In embodiments, a reference subject is a healthy subject. In embodiments, a reference subject is an untreated subject having sepsis. In embodiments, a reference subject is a healthy subject. The term “sepsis” refers to a medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) associated with a severe infection. Sepsis is commonly caused by the immune system's response to a serious infection, (e.g., from bacteria, fungi, viruses, and parasites in the blood, urinary tract, lungs, skin, or other tissues). Indications of sepsis can range from infection to multiple organ dysfunction syndrome. Common symptoms of sepsis include those related to a specific infection, but usually accompanied by high fevers, hot, flushed skin, elevated heart rate, hyperventilation, altered mental status, swelling, and low blood pressure. By "subject" or “patient” is meant a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline. In some embodiments, the subject is a human. The terms “subject” and “patient” are used interchangeably herein. By "substantially identical" is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In an embodiment, such a sequence is at least 60%, more preferably 80% or 85%, and 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 approach to determining the degree of identity, a BLAST program may be used, with a probability score between e-3and e-100indicating a closely related sequence. Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. As used herein, the terms “treat,” treating,” “treatment,” and the like refer to reducing or ameliorating a disorder and / or symptoms associated therewith. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated. In some embodiments, a treatment for sepsis can include treating a subject to prevent the sepsis. Unless specifically stated or obvious from context, as used herein, the term "or" is understood to be inclusive. Unless specifically stated or obvious from context, as used herein, the terms "a", "an", and "the" are understood to be singular or plural. Unless specifically stated or obvious from context, as used herein, the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. About can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about. The recitation of an embodiment for a variable or aspect herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein. DETAILED DESCRIPTION OF THE DISCLOSURE The disclosure features compositions and methods for treatment of sepsis in a subject. The disclosure is based, at least in part, on the discovery of small molecules having CD11c agonist activity in cell adhesion assays and a pre-selected high throughput screening process. Accordingly, provided herein are CD11c agonists and methods of using said agonists to treat or ameliorate one or more symptoms of sepsis. To date, the failure of the drug discovery campaign for sepsis is mainly due to the lack of knowledge regarding sepsis pathophysiology and the usage of inappropriate strategies for drug development. For example, anti-inflammatory treatments for sepsis that act by blocking pro- Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 inflammatory cytokines are one conventional strategy. However, this strategy is ineffective because systemic inflammatory response syndrome (SIRS) is not a fundamental characteristic of sepsis, as recently pointed out (Dejager et al., Trends Microbiol 19, 198-208 (2011)). Because the first-line responder cells, neutrophils, are dysfunctional in sepsis, granulocyte colony- stimulating factor (G-CSF) treatment was undertaken to increase neutrophil number in a different approach. This approach was not effective because it mobilized largely immature neutrophils that were less functional compared to mature neutrophils (Bo et al., Crit Care 15, R58 (2011); Knudsen et al., Eur J Haematol 87, 302-311 (2011); Basu et al., Blood 100, 854-861 (2002)). Without intending to be bound by theory, it is an important insight of the present disclosure that an intervention to actively enhance neutrophil maturation is important for the improvement of sepsis outcome. Sepsis Sepsis and septic shock are associated with activation of the innate immunity and coagulation systems. Sepsis and septic shock are characterized clinically by systemic inflammation, coagulopathy, hypotension and multiple organ dysfunction (J.-L. Vincent et al., Annuals of Medicine 34 (2002) 606-613). During severe sepsis, a network of specific proteases activates clotting, fibrinolytic and complement factors. These proteases can also trigger tissue and organ damage and enhance non-specific proteolysis of clotting and complement factors in plasma (J. Wite et al., Intensive Care Medicine 8 (1982) 215-222; S. J. Weiss, New England Journal of Medicine 320 (1989) 365-376). "Sepsis-like" symptoms are observed in the exposed individuals mainly due to the overwhelming systemic inflammatory response of the body. The overreaction typically includes excessive production of cytokines ("cytokine storm") and destructive proteases and disturbances in metabolic, oxygenation, coagulation, and vascular functions leading to multi-organ dysfunction. Symptoms of sepsis may include, without limitation: damage to tissues, suppression of the immune system, fever, increased heart rate, increased breathing rate, and confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. The very young, old, and people with a weakened immune system may have no symptoms of a specific infection, and the body temperature may be low or normal instead of having a fever. Severe sepsis causes poor organ function or blood flow. The presence of low blood pressure, high blood lactate, or low urine output may suggest poor blood flow. Sepsis may lead to septic shock. Septic shock is characterized by low blood pressure due to sepsis that does not improve after fluid replacement. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Sepsis was originally defined in 1991 as a type of infection associated with systemic inflammatory response syndrome (SIRS). Based on this definition, a number of studies profiled plasma pro-inflammatory mediators during sepsis. Many pharmaceutical companies considered cytokines to be therapeutic targets and invested in anti-cytokine therapies. However, they did not work out well in clinical trials. In the most recent conference (Sepsis 3 conference), SIRS was no longer considered a requirement of sepsis. Patients with sepsis still suffer from high morbidity and mortality. Sepsis is responsible for a significant health care cost. Thus, it is urgently needed to develop a therapeutic tool specific to sepsis. Host immune dysfunction is a well-recognized signature in sepsis. Neutrophils are critical first-line defense innate immune cells equipped with a number of antimicrobial tools. Because they are remarkably shortest-lived among leukocytes, with a circulating half-life of 6-8 hours, the BM continues to produce mature neutrophils from hematopoietic stem cells, with granulocyte-monocyte progenitor cells (GMPs), pre-neutrophils to immature (banded) neutrophils in transition. In an immune-steady state, mature neutrophils are released into circulation. In sepsis, exaggerated de novo neutrophil generation is induced largely by G-CSF, which is highly produced during infection. To meet a demand, however, pre- neutrophils / immature neutrophils are also released into a circulation and occupy a significantly high percentage of blood neutrophils in septic patients, and despite their effector functions these cells are not mature. G-CSF has been widely administered to neutropenic patients due to their known effect to stimulate neutrophil production but it itself does not contribute to neutrophil maturation10,11. Not unexpectedly G-CSF therapy did not improve sepsis mortality in non- neutropenic cohorts (Bo et al., Crit Care 15, R58 (2011); Knudsen et al., Eur J Haematol 87, 302- 311 (2011); Basu et al., Blood 100, 854-861 (2002)). An intervention to actively enhance neutrophil maturation is critical for better effector functions. CD11c CD11c / CD18 (CD11c; also called αXβ2, complement receptor 4) is a member of the leukocyte adhesion molecule β2 integrins, and is primarily considered to be a marker of dendritic cells (DCs) (Sandor, N. et al., PLoS One 11, e0163120 (2016)). In a clinical study, the presence of a high percentage of CD11c-expressing blood neutrophils on their cell surface was a marker to differentiate sepsis from sterile SIRS (Lewis, S. M. et al., Clin Exp Immunol 182, 184-194, (2015)). Cell surface CD11c positive neutrophil population also emerged in the peripheral blood of murine sepsis models. It was previously shown that CD11c knock Out (KO) mice had decreased survival in polymicrobial sepsis induced by cecal ligation and puncture (CLP) surgery Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 (Hou et al., Blood Adv 4, 6086-6097 (2020)). In addition, CD11c KO mice demonstrated worse bacterial clearance in both Escherichia coli (E. coli) sepsis and CLP sepsis. It was unexpectedly found that CD11c was expressed in bone marrow (BM) neutrophils (predominantly expressed intracellularly) and its deficiency was associated with impaired neutrophil maturation in both BM and peripheral blood. β2 integrins bind to their ligands for their functional output only when activated. Constitutively active CD11c knock-in (KI) mice were generated, which had more mature neutrophils in the BM compared to WT mice along with better bacterial clearance and improved survival following the experimental sepsis. To date there are no known compounds to modulate CD11c function. Thus, provided herein are CD11c agonists that when administered to a subject having or having a propensity to develop sepsis show enhanced neutrophil maturation, resulting in improved effector functions and sepsis outcome. Methods of Treatment In one aspect the disclosure provides a method for treating sepsis in a subject. The methods herein include administering to the subject (including a subject identified as in need of such treatment) an effective amount of an agent, or a composition to produce a desired effect (e.g., treatment of sepsis). The agent can be a CD11c agonist. Identifying a subject in need of such treatment can be in the judgment of a subject or a health care professional and can be subjective (e.g. opinion) or objective (e.g. measurable by a test or diagnostic method). The therapeutic methods of the disclosure (which include prophylactic treatments) in general comprise administration of a therapeutically effective amount of an agent for treatment of sepsis to a subject (e.g., animal, human) in need thereof, including a mammal, particularly a human. Such treatment will be suitably administered to subjects, particularly humans, suffering from, having, susceptible to, or at risk for a disease, or symptom thereof. In another aspect, the present disclosure provides methods of promoting maturation of neutrophils (e.g., in a subject). These methods involve contacting a neutrophil (e.g., in a subject in need thereof) with an agent of the present disclosure (e.g., a CD11c agonist). In another aspect, the present disclosure provides methods of increasing bacterial clearance (e.g., in a subject). In embodiments, the subject may have a bacterial infection and / or sepsis. These methods involve contacting a neutrophil (e.g., in a subject in need thereof) with an agent of the present disclosure (e.g., a CD11c agonist). In another aspect, the present disclosure provides methods of improving survival of a subject having a bacterial infection. In embodiments, the subject may have sepsis. These Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 methods involve contacting a neutrophil (e.g., in a subject in need thereof) with an agent of the present disclosure (e.g., a CD11c agonist). In another aspect, the present disclosure provides methods of immune modulation (e.g., in a subject). These methods involve contacting a neutrophil (e.g., in a subject in need thereof) with an agent of the present disclosure (e.g., a CD11c agonist or antagonist). The examples provided herein demonstrate that agents disclosed herein (e.g., CD11c agonists) were able to activate and / or upregulate CD11c. In embodiments, the methods provided herein are effective to ameliorate one or more symptoms of sepsis, such as, but not limited to, damage to tissues, suppression of the immune system, fever, increased heart rate, increased breathing rate, and confusion. In embodiments, the methods of the present disclosure promote neutrophil maturation (e.g., of a subject in need thereof). Administration may be affected continuously or intermittently, and parenterally. A composition can be administered locally (e.g., intratumoral) or systemically (e.g., intravenously). Administration may be for treating a subject already confirmed as having a recognized condition, disease or disease state, or for treating a subject susceptible to or at risk of developing such a condition, disease or disease state. Co-administration with an adjunctive therapy may include simultaneous or sequential delivery of multiple agents in any order and on any dosing schedule. The methods herein include administering to the subject (including a subject identified as in need of such treatment) an effective amount of a pharmaceutical composition to produce a treatment or preventative effect. The therapeutic methods of the disclosure in general comprise administration of a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof, including a mammal, particularly a human. Treatment will be suitably administered to subjects, particularly humans, suffering from, having, susceptible to, or at risk for sepsis, or symptom thereof. Determination of those subjects "at risk" can be made according to the judgment of a subject or a health care professional. Pharmaceutical Compositions Agents of the present disclosure (e.g., CD11c agonists or antagonists), can be incorporated into a variety of formulations for therapeutic use (e.g., by administration) or in the manufacture of a medicament (e.g., for treating sepsis) by combining the agents with appropriate pharmaceutically acceptable carriers or diluents, and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms. Examples of such formulations include, without limitation, tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, gels, microspheres, and aerosols. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Pharmaceutical compositions provided herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include the steps of bringing the agent or agents provided herein (e.g., a CD11c agonist), i.e., the “active ingredient”, into association with a carrier or excipient, and / or one or more other accessory ingredients, and then, if necessary and / or desirable, shaping, and / or packaging the product into a desired single- or multi-dose unit. Within the scope of this disclosure is a composition that contains a suitable carrier and one or more of the therapeutic agents described above. The composition can be a pharmaceutical composition that contains a pharmaceutically acceptable carrier, a dietary composition that contains a dietarily acceptable suitable carrier, or a cosmetic composition that contains a cosmetically acceptable carrier. The term “pharmaceutical composition” refers to the combination of an active agent with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo, or ex vivo. A “pharmaceutically acceptable carrier,” after administered to or upon a subject, does not cause undesirable physiological effects. The carrier in the pharmaceutical composition must be “acceptable” also in the sense that it is compatible with the active ingredient and can be capable of stabilizing it. One or more solubilizing agents can be utilized as pharmaceutical carriers for delivery of an active compound or agent. Examples of a pharmaceutically acceptable carrier include, but are not limited to, biocompatible vehicles, adjuvants, additives, and diluents to achieve a composition usable as a dosage form. Examples of other carriers include colloidal silicon oxide, magnesium stearate, cellulose, sodium lauryl sulfate, and D&C Yellow # 10. Pharmaceutically acceptable salts are salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, or allergic response, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts of amines, carboxylic acids, and other types of compounds and agents, are well known in the art. For example, S.M. Berge, et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1-19 (1977), incorporated herein by reference. The salts can be prepared in situ during the final isolation and purification of the agents of the disclosure, or separately by reacting a free base or free acid function with a suitable reagent, as described generally below. For example, a free base function can be reacted with a suitable acid. Furthermore, where the agents of the disclosure carry an acidic moiety, suitable pharmaceutically acceptable salts thereof may, include metal salts such as alkali metal salts, e.g. sodium or potassium salts; and alkaline earth metal salts, e.g. calcium or Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 magnesium salts. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts, include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphor sulfonate, citrate, cyclopentane propionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, and valerate salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, alkyl sulfonate and aryl sulfonate. As described above, the pharmaceutical compositions of the present disclosure additionally include a pharmaceutically acceptable carrier, which, as used herein, includes any and all solvents, diluents, or other liquid vehicle, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, and lubricants, as suited to the particular dosage form desired. Remington’s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in formulating pharmaceutical compositions and known techniques for the preparation thereof. Except insofar as any conventional carrier medium is incompatible with the agents of the disclosure, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutical composition, its use is contemplated to be within the scope of this disclosure. Some examples of materials which can serve as pharmaceutically acceptable carriers include, but are not limited to, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatine; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil, sesame oil; olive oil; corn oil and soybean oil; glycols; such as propylene glycol; esters such as ethyl oleate and ethyl Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 laurate; agar; natural and synthetic phospholipids, such as soybean and egg yolk phosphatides, lecithin, hydrogenated soy lecithin, dimyristoyl lecithin, dipalmitoyl lecithin, distearoyl lecithin, dioleoyl lecithin, hydroxylated lecithin, lysophosphatidylcholine, cardiolipin, sphingomyelin, phosphatidylcholine, phosphatidyl ethanolamine, diastearoyl phosphatidylethanolamine (DSPE) and its pegylated esters, such as DSPE-PEG750 and, DSPE-PEG2000, phosphatidic acid, phosphatidyl glycerol and phosphatidyl serine. Commercial grades of lecithin which are preferred include those which are available under the trade name Phosal® or Phospholipon® and include Phosal 53 MCT, Phosal 50 PG, Phosal 75 SA, Phospholipon 90H, Phospholipon 90G and Phospholipon 90 NG; soy-phosphatidylcholine (SoyPC) and DSPE-PEG2000 are particularly preferred; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. A pharmaceutical composition of this disclosure can be administered parenterally in some embodiments. The term “parenteral” as used herein refers to subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional, or intracranial injection, as well as any suitable infusion technique. A sterile injectable composition can be a solution or suspension in a non-toxic parenterally acceptable diluent or solvent. Such solutions include, but are not limited to, 1,3- butanediol, mannitol, water, Ringer’s solution, and isotonic sodium chloride solution. In addition, fixed oils are conventionally employed as a solvent or suspending medium (e.g., synthetic mono- or diglycerides). Fatty acid, such as, but not limited to, oleic acid and its glyceride derivatives, are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as, but not limited to, olive oil or castor oil, polyoxyethylated versions thereof. These oil solutions or suspensions also can contain a long chain alcohol diluent or dispersant such as, but not limited to, carboxymethyl cellulose, or similar dispersing agents. Other commonly used surfactants, such as, but not limited to, Tweens or Spans or other similar emulsifying agents or bioavailability enhancers, which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms also can be used for the purpose of formulation. The compositions can contain auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, colors, and the like, depending upon the route of Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 administration and the preparation desired. Standard texts, such as “Remington's Pharmaceutical Science,” 17th edition, 1985, incorporated herein by reference, may be consulted to prepare suitable preparations, without undue experimentation. Pharmaceutical compositions may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The agents may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. In some embodiments of any of the aspects, the formulation comprising a compound / agent comprises one or more additional components, wherein the additional component is at least one of an osmolar component that provides an isotonic, or near isotonic solution compatible with human cells or blood, and a preservative. Additives that enhance the stability and sterility of the compositions, including antimicrobial preservatives, antioxidants, chelating agents, and buffers, can be added. Prevention of the action of microorganisms can be ensured by an antibacterial or antifungal agent including, but not limited to, parabens, chlorobutanol, phenol, and sorbic acid. According to the present disclosure, however, any vehicle, diluent, or additive used must be compatible with the cells. In some embodiments of any of the aspects, the osmolar component is a salt, such as sodium chloride, or a sugar or a combination of two or more of these components. In some embodiments of any of the aspects, the sugar may be a monosaccharide such as dextrose, a disaccharide such as sucrose or lactose, a polysaccharide such as dextran 40, dextran 60, or starch, or a sugar alcohol such as mannitol. The osmolar component is readily selected by those skilled in the art. In some embodiments of any of the aspects, the preservative is at least one of parabens, chlorobutanol, phenol, sorbic acid, and thimerosal. Viscosity of the compositions, if desired, can be maintained at a selected level using a pharmaceutically acceptable thickening agent. In some embodiments, the thickening agent is methylcellulose, which is readily and economically available and is easy to work with. Other suitable thickening agents include, but are not limited to, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose, and carbomer. The concentration of the thickener will depend upon the agent selected and the amount of the agent used. Suitable carriers and other additives may be chosen depending on the route of administration and the nature of the dosage form (e.g., a liquid Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 dosage form can be formulated into a solution, a suspension, a gel, or another liquid form, such as a time release formulation or liquid-filled form). In some embodiments of any of the aspects, the formulation comprising an agent is in the form of a sustained release formulation. The skilled artisan can readily determine the amounts of the active ingredient (e.g., a CD11c agonist), and optional additives, vehicles, and / or carrier in compositions to be administered. For any composition to be administered to an animal or human, and for any particular method of administration, toxicity can be determined by measuring the lethal dose (LD) and LD50 in a suitable animal model, e.g., a rodent such as mouse. The dosage of the composition(s), concentration of components therein, and timing of administering the composition(s), which elicit a suitable response can also be determined. Such determinations do not require undue experimentation in light of the knowledge of the skilled artisan, this disclosure, and the documents cited herein. The time for sequential administrations can also be ascertained without undue experimentation. It will also be understood that, if desired, the compositions of the invention may be administered in combination with other agents as well, such as, e.g., other proteins, polypeptides, small molecules or various pharmaceutically-active agents (e.g., granulocyte colony-stimulating factor (G-CSF)). There is virtually no limit to other components that may also be included in the compositions, provided that the additional agents do not adversely affect the ability of the composition to deliver the intended gene therapy. In the pharmaceutical compositions of the invention, formulation of pharmaceutically- acceptable excipients and carrier solutions is well-known to those of skill in the art, as is the development of suitable dosing and treatment regimens for using the particular compositions described herein in a variety of treatment regimens, including e.g., oral, parenteral, intravenous, intranasal, and intramuscular administration and formulation. Particular embodiments of the invention may comprise other formulations, such as those that are well known in the pharmaceutical art, and are described, for example, in Remington: The Science and Practice of Pharmacy, 20th Edition. Baltimore, MD: Lippincott Williams & Wilkins, 2000. Combination Therapies Optionally, an agent disclosed herein (e.g., a CD11c agonist), may be administered together with any other standard treatment for sepsis, including but not limited to, granulocyte colony-stimulating factor (G-CSF), antibiotics, and / or appropriate antibodies. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Accordingly, in an aspect, the present disclosure provides a pharmaceutical composition comprising an agent disclosed herein (e.g., a CD11c agonist) and G-CSF. In embodiments, the agents may be formulated together or separately. Kits The disclosure provides kits for treating sepsis. The kits may include a therapeutic composition comprising one or more agents described herein for treating sepsis. In some embodiments, the agent is a small molecule CD11c agonist. In some embodiments, the kit comprises a sterile container which contains a pharmaceutical composition; such containers can be boxes, ampoules, bottles, vials, tubes, bags, pouches, blister-packs, or other suitable container forms known in the art. Such containers can be made of plastic, glass, laminated paper, metal foil, or other materials suitable for holding medicaments. If desired, the kit further comprises instructions for administering a pharmaceutical composition to a subject in need thereof (e.g., a subject having sepsis). In particular embodiments, the instructions include at least one of the following: description of the therapeutic agent; dosage schedule and administration for reducing sepsis symptoms; precautions; warnings; indications; counter-indications; over dosage information; adverse reactions; animal pharmacology; clinical studies; instructions on how to assess subject risk for disease or disorder; and / or references. The instructions may be printed directly on the container (when present), or as a label applied to the container, or as a separate sheet, pamphlet, card, or folder supplied in or with the container. The instructions can be provided in digital form on a portable data storage medium (e.g., a compact disk or USB drive) or stored remotely on a server that can be accessed remotely. The practice of the present disclosure employs, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are well within the purview of the skilled artisan. Such techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, second edition (Sambrook, 1989); “Oligonucleotide Synthesis” (Gait, 1984); “Animal Cell Culture” (Freshney, 1987); “Methods in Enzymology” “Handbook of Experimental Immunology” (Weir, 1996); “Gene Transfer Vectors for Mammalian Cells” (Miller and Calos, 1987); “Current Protocols in Molecular Biology” (Ausubel, 1987); “PCR: The Polymerase Chain Reaction”, (Mullis, 1994); “Current Protocols in Immunology” (Coligan, 1991). These techniques are applicable to the production of the polynucleotides and polypeptides of the Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 disclosure, and, as such, may be considered in making and practicing the disclosure. Particularly useful techniques for particular embodiments will be discussed in the sections that follow. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the assay, screening, and therapeutic methods of the disclosure, and are not intended to limit the scope of what the inventors regard as their disclosure. EXAMPLES Example 1: Screening assay for CD11c agonists and antagonists The β2 integrins are cell adhesion molecules with non-covalently associated α- (CD11a- d) and β-(CD18) subunits and exclusively expressed on leukocytes. The intracellular signal activates β2 integrins (inside-out signal), which leads into their ligand binding. Once they bind to their ligands, they induce intracellular signals (outside-in signal) for cytoskeletal arrangement. CD11c / CD18 is a type I transmembrane protein composed of a large extracellular segment, a single transmembrane segment, and a short cytoplasmic tail. The top domain of CD11c (α subunit) is called the αI domain and serves as a ligand binding domain, whereas other domains play regulatory roles. The top domain of CD18 (β subunit) is called the βI domain, which is structurally homologous to the αI domain. The ability of the αI domain to bind to its ligand is controlled by conformational changes. The affinity of the αI domain to bind to its ligand is enhanced by a piston-like downward axial displacement of its C-terminal α7 helix, which is induced by conformational signals relayed from the βI domain that receive inside-out signal to the αI domain via inter-domain interactions derived from polar interaction. Throughout this process, CD11c / CD18 undergoes a significant conformational change from the bent (inactivated, low-affinity) to the extended (activated, high-affinity) conformation. HEK cells stably expressing WT CD11c / CD18 were created. This stable cell line was used to test the effect of screened small molecules on CD11c function and specificity. A binding assay was performed using a V-bottom assay. HEK cells stably expressing CD11c / CD18 WT were stained with carboxyfluorescein acetoxylmethy ester and incubated on V-bottom wells coated with CD11c ligand iC3b at 10 mM EDTA (no binding condition), 1 mM Mg2+ / Ca2+(non-activation condition), or 1 mM Mn2+(activation condition) in the presence or absence of the small molecules screened. Following incubation for 30 minutes, plates were centrifuged at 500 x g and subjected to fluorescence reading (readout is Mean Fluorescence Intensity (MFI)). Binding % was defined as ((MFI of cells with EDTA) – (MFI of cells with Mg / Ca or with Mn)) / (MFI of cells with EDTA) x 100(%). Minimal binding in the Mg2+ / Ca2+ Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 condition, and significant binding in Mn2+condition was expected, respectively. When more than a 50% increase in binding % was observed in Mg / Ca2+condition, the compound was considered to be a CD11c agonist. When more than a 50% decrease in binding% was observed in Mn2+condition, the compound was considered to be a CD11c antagonist. 38 CD11c agonist hits were discovered. The results of this screening is provided in Table 1 and Table 2 below. Table 1: CD11c Agonists Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Table 2: CD11c Antagonists Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Example 2: Determination of compound efficacy of selected compounds This study includes the determination of in vitro and in vivo efficacy and toxicity experiments for CD11c agonists. Combining the in vitro EC50and in vitro toxicity on certain primary and cell lines, the top 3 hits are selected for further in vivo toxicity and efficacy evaluations; the acute in vivo toxicity study (single dose toxicity study) is executed in mice to have the LD50information of 3 hits, which is the foundation for the dosage for the in vivo efficacy study. The in vivo efficacy is evaluated by treating the septic model mice with hits in high, medium and low doses, in both prophylactic and therapeutic manners. Combining the in vitro EC50, in vitro CC50, in vivo LD50and pharmacological efficacy and dose-dependence, top hit is chosen for further experimentation. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Experimental Design: A) In vitro study to determine the EC50 of compounds to activate CD11c. B) In vitro study to determine the toxicity of agonists against several primary cells and cell lines, including human peripheral blood neutrophils, HL-60 cell line, and HEPG2 cell line (liver cell); C) Prepare the e-coli stock for in vivo model. Mice are i.v injected with E-coli to to induce bacterial induced sepsis, which could be standardized and is more stable than surgery induced sepsis (CLP). D) Single dose toxicity (acute toxicity) in mouse. EC50 of CD11c agonist and CC50 results are combined on primary cell and cell lines to choose top 3 compounds. Then naïve mice are used to acquire the LD50, which is the foundation to determine the initial doses for efficacy study in disease models. E) In vivo efficacy study. Based on LD50 information, each compound will be tested in vivo on 3 doses (high, medium and low doses), which will be 1 / 10, 1 / 30 and 1 / 90 of LD50accordingly. In vivo model will be E. coli induced sepsis. Treatment will be both prophylactic (one treatment per day, continuous 5 days before inducing sepsis) and therapeutic (0, 12, 24 and 48 hours post sepsis induction). In embodiments, treatment route will be oral or intravenous. Efficacy readout will be body weight change (measured every day for 7 days), survival rate, blood bacteremia analysis (end point), bone marrow and blood neutrophil counts and phenotyping (maturation status) The in vitro EC50, in vitro CC50, in vivo LD50and pharmacological efficacy and dose- dependence results are combined, and the top hit is chosen for further study. Neutrophils are the first line defense to fight the invading pathogen. During this process, neutrophils fight against microbes through various strategies, including phagocytosis, releasing extracellular traps (NETs), and producing ROS to inactivate, digest, and eventually eliminate the pathogen. Once pathogens are eliminated, inflammation will be resolved and immune homeostasis will be recovered. Under sepsis condition, a large amount of immature neutrophils with compromised function are emergently mobilized from the bone marrow and enter the peripheral blood to fight the pathogen. However, the compromised function of immature neutrophils, regardless of the increased number, make the immune defense inefficient, and the inflammation continues and the pathogen persists. Thus, without intending to be bound by theory, instead of further increasing neutrophil number like G-CSF, enhancing the maturation and function of neutrophils is a promising strategy to solve the sepsis condition and maintain the immune homeostasis. Without intending to be bound by theory, CD11c agonists are expected to Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 treat and / or reduce a symptom of sepsis by, at least in part, enhancing the maturation of neutrophils and / or enhancing the function of neutrophils, and / or facilitating in the enhancement of either of the aforementioned functions. In vitro efficacy and cytotoxicity analysis. All 38 CD11c agonists are further screened by cell adhesion assay with various concentrations ranging from 10 µM to 1 nM with 10-fold dilution. After initial screening, the second round of screening is executed with three-fold dilution with relatively narrowed concentration range, and then EC50 will be calculated accurately. In parallel, cytotoxicity assay through MTT method will be done in non-transfected HEK cells, and CC50 will be calculated as well. Since the major target cell in vivo is neutrophils, the cytotoxicity is tested against freshly isolated human neutrophils as well. Furthermore, human hepatocyte cell line HepG2 will be used here to test the cytotoxicity of compounds against HepG2 cells. The selectivity index (SI, = CC50 / EC50) is used as the toxicity versus efficacy index to rank and choose all the bioactive hits. Traditionally, a compound with SI≥3 is deemed as a bioactive molecule with high selectivity (Prayong et al., Fitoterapia 79, 598-601 (2008)), which will be applied in this study as well. Since the EC50 is determined according to in vitro adhesion assay, the on-target efficacy of CD11c agonist on HL-60 cell differentiation into neutrophil is further verified in vitro. In this case, HL-60 cells will be differentiated with 1 µM all-trans retinoic acid (ATRA) and 1.25% DMSO for 4 days (Hou, L. et al., Blood Adv 7, 1312-1325, (2023)) in the presence or absence of CD11c agonist with 3 concentrations- 3xEC50, EC50 and 1 / 3 EC50. The readout will be the increased expression of CD11b, a marker for terminally differentiated neutrophils. Human subject power calculation Toxicity will be checked with triplicates 47 compounds will be tested with different concentrations. Given at least 1 x103neutrophils / µL, and 105neutrophils per well x 5 conditions x 3 replicates x 47 compounds = 7.0 x 107neutrophils, thus requiring 70 mL of blood. With 10 mL per healthy donor, 7-8 healthy donors will be used. Results Top 3 hits with the best profile with SI at least ≥3 are identified. CD11c agonist is able to accelerate the HL-60 differentiation into neutrophil in a concentration-dependent manner. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 If CD11c agonist are not able to further enhance HL-60 differentiation into neutrophils the protocol is modified by adding the CD11c agonist alone or in combination with all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO) respectively. In vivo acute toxicity study The top 3 hits will be further tested in vivo for acute toxicity and other toxicity profiles, which will serve as foundation for choosing the reasonable doses for in vivo pharmacology studies. Considering the 3R principle and the suspension (deletion) of the conventional LD50tests in 2002 by OECD, the up and down procedure (UDP) will be used, which was introduced in 1998 and also recommended in the field and regulatory agency (Lichtman, J Pharmacol Toxicol Methods 40, 81-85 (1998); Chinedu et al., Toxicol Int 20, 224-226, (2013)). In detail, individual mice will be tested sequentially, with the dose for each animal being regulated up or down based on the results of the preceding tests. The starting dose will be 2000 mg / kg bodyweight. Mice will be dosed one at a time, at a 48-hour interval. Each mouse will be carefully observed for 48 hours, and all details recorded. Decision of the next mouse and its dose will be decided based on the previous mouse and dose. The dose for the next animal is increased by a factor of 3.2 if the preceding animal survives, while the dose is decreased by a factor of 3.2 if the animal dies. Experiment will be terminated when 3 consecutive mice survive. The LD50will be calculated by using the software AOT425StatPgm developed by US Environmental Protection Agency (EPA). Power calculation Compared with the “classic” procedure, the up and down procedure (UDP) for acute toxicity study permits a dramatic reduction in the number of animals used, which requires up to 10 mice to roughly calculate the LD50. To achieve the accuracy, the UDP will be repeated 3 times for each hit to allow statistical calculation with 20% standard deviation at 5% significance. Thus, 90 mice will be needed for 3 hits. Results The up and down method is widely used method to achieve LD50, and is particularly useful for testing toxic compounds. Mice will be treated with the compound through i.v. injection, in which case the absolute bioavailability is high and most likely will induce an acute toxicology reaction in mouse. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 In clinical practice for sepsis treatment, patients are usually treated through i.v. Thus, mice will be treated with CD11c agonists through i.v. as well. I.p injection may be used as an alternative for i.v. injection if solubility issues arise. Example 3: Further characterization of selected compound In this study, the efficacy of the top CD11c agonist hit (“top hit”) will be comprehensively evaluated, alone and in combination with granulocyte colony-stimulating factor (G-CSF), in treating various sepsis models (E.coli-induced-, P. aureus-induced-, and S. aureus- induced sepsis). The solubility, plasma protein binding, preliminary in vitro ADME, off-target effects (mainly hERG at this stage), and single dose pharmacokinetics will be evaluated in both mouse and rat models. Since sepsis is acute and the treatment is usually shorter than two weeks, pilot multi-dose toxicity (one-month long-term toxicity study, and resting for additional one month without treatment) in non-GLP condition will be performed. The main goal in this study is to 1) continuously explore the efficacy of the top hit in treating sepsis by including E. coli, P. aeruginosa, S. aureus- sepsis models; 2) explore the efficacy of the top hit in combination with existing therapeutics, particularly G-CSF; 3) provide the direction for further structural optimization of the top hit. Experimental Design: A) Single usage and in combination with G-CSF in treating sepsis models, which will include all of E. coli induced sepsis, P. aeruginosa induced sepsis and S. aureus induced sepsis. High, medium and low doses will be chosen when the top hit will be used alone. Currently, G-CSF is in clinical usage for sepsis patient by emergently mobilizing neutrophil. However, since these emergently mobilized neutrophils are less mature and cannot function properly, the clinical benefit of G-CSF has been largely compromised. Since the MOA of CD11c agonist is to induce neutrophil maturation, we hypothesize that CD11c agonist in combination with G-CSF will be promising and might be able to decrease the dose of G-CSF. In case of combination with G-CSF, high dose of the top hit will be used. G-CSF dose will be varied. Treatment will be both prophylactic (one treatment per day, continuous 5 days before inducing sepsis) and therapeutic (0, 12, 24 and 48 hours post sepsis induction). B) Determine the solubility, plasma protein binding, ADME (absorption, distribution, metabolism and excretion). Regarding the preliminary ADME study, the metabolic stability will be tested through liver microsome (all of human, mouse and rat), and Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 CYP450 inhibition (Cytochrome P450 proteins, including all of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) will be tested; absorption and permeability will be tested through caco-2 cells. C) Off-target analysis. The top hit will be tested on around 90 kinases, ion channels (hERG, hCav1.2, hNav1.5, hKCNQ1 / mink, hKv4.3 / KChIP2.2, hKir2.1) and 100 GPCRs. D) Preclinical non-GLP toxicity study. Since sepsis is acute and the treatment is usually shorter than two weeks, a pilot multi-dose toxicity (one-month long-term toxicity study, and resting for additional one month without treatment) will be performed in non-GLP condition. Four groups of rats will be treated with vehicle and high, medium and low dose of the top hit. Half of the rats will be sacrificed at one-month post treatment, and rats will be dissected, and main tissues will be collected for histology evaluation. Both anticoagulated blood and plasma will be collected for blood cell phenotyping and blood biochemistry analysis. One month later, the rest rats will be sacrificed, and the above experiments will be repeated. Pharmacokinetic study (PK) study. A pilot single dose PK study will be done in both mouse and rat. Treatment will be both p.o and i.v. Dose selection is that will be high dose is for p.o, and medium dose is for i.v. T1 / 2, Tmax, Cmax, AUClast (h*ng / ml), Vss_obs (ml / kg), CL_obs (ml / min / kg) and then bioavaibility (p.o) will be calculated. There are several sepsis mouse models including LPS-injection induced sepsis, CLP induced sepsis and E. coli-injection induced sepsis. Considering the mechanism of CD11c agonist, and the reproducibility of model, E. coli-injection induced sepsis will be used for in vivo drug efficacy screening. Based on LD50 information, each compound will be tested in vivo on 3 doses (high, medium and low doses), which will be 1 / 10, 1 / 30 and 1 / 90 of LD50 accordingly. Examination of the efficacy of CD11c agonist treatment alone. Septic mice will be treated with top 3 hits in high, medium and low doses. Treatment will be both prophylactic (one treatment per day, continuous 5 days before inducing sepsis) and therapeutic (0, 12, 24 and 48 hours post sepsis induction). Examination of the efficacy of CD11c agonist in combination with G-CSF. Septic mice will be treated with G-CSF alone or together with 3 hits in high dose only, in both prophylactic and therapeutic manners. Treatment will be both prophylactic (one treatment per day, continuous 5 days before inducing sepsis) and therapeutic (0, 12, 24 and 48 hours post sepsis induction). Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Survival rate and body weight change will be monitored and evaluated as treatment outcome. Peripheral blood will be collected at 4 hours ahead of sepsis induction (prophylactic treatment) or at day 2 post sepsis induction (therapeutic treatment) through tail nick; neutrophil number and maturation status will be checked, as the on-target validation for CD11c agonist. The maturation status will be measured through the surface expression of CD11b and CXCR2. Cell number will be countered by using the counting beads. An E. coli-induced septic model will be used for in vivo pharmacology study. Septic mice will be treated with top 3 hits in high, medium and low doses, in both prophylactic and therapeutic manners. Separately, septic mice will be treated with G-CSF alone or together with 3 hits in high dose only, in both prophylactic and therapeutic manners. In both settings, survival rate and body weight change will be monitored and evaluated as treatment outcome. In the later setting, peripheral blood will be collected through tail nick and neutrophil number and maturation status will be checked, as the on-target validation for CD11c agonist. Power calculation Based on statistical calculations to detect a 30% difference in survival with 20% standard deviation at 5% significance and 80% power and the results, 6 mice per group will be used for statistical comparison. Thus, 360 mice will be needed. Results Considering the high risk of novel drug development and the urgent need for therapeutics treating sepsis patient, the high dose of the top hit should be able to significantly increase the survival rate of septic mice. This should also significantly protect mice from sepsis in the prophylactic treatment. The potency, selectivity, and physical-chemical properties of the selected hits will also be improved. This may involve structural modifications, exploring structure-activity relationships (SAR), incorporating computational modeling (such as fragment-based or structure-based drug design), and leveraging medicinal chemistry principles to guide the design of new compounds. A series of analogs of the hit compounds will be synthesized based on the design strategies. This will help to understand how different modifications affect the compound's biological activity, selectivity, and other properties to establish the SAR. SARs are refined based on the data obtained from the biological assays including potency, selectivity, and other relevant pharmacological properties. Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 Other Embodiments From the foregoing description, it will be apparent that variations and modifications may be made to the invention described herein to adopt it to various usages and conditions. Such embodiments are also within the scope of the following claims. The recitation of a listing of elements in any definition of a variable herein includes definitions of that variable as any single element or combination (or subcombination) of listed elements. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. All patents and publications mentioned in this specification are herein incorporated by reference to the same extent as if each independent patent and publication was specifically and individually indicated to be incorporated by reference.

Claims

Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 What is claimed is:

1. A method of inducing neutrophil maturation, the method comprising contacting a neutrophil with a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, thereby inducing neutrophil maturation.

2. The method of claim 1, wherein the neutrophil is in vitro or in vivo.

3. A method of inducing neutrophil mobilization and maturation in a subject, the method comprising administering to the subject granulocyte colony-stimulating factor (G-CSF) and a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)- 10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro- 1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4-Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, wherein the CD11c agonist and the G-CSF are administered sequentially or concurrently, thereby inducing neutrophil mobilization and maturation in the subject.

4. The method of claim 3, wherein the G-CSF is administered prior to the CD11c agonist.

5. A method of enhancing an immune response in a subject, the method comprising administering to the subject a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, thereby enhancing an immune response in the subject.Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 6. The method of claim 3 or 5, wherein the subject has a bacterial infection and / or sepsis.

7. A method of treating sepsis in a subject in need thereof, the method comprising administering to the subject a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, thereby, thereby treating the sepsis.

8. The method of claim 7, further comprising administering a granulocyte colony- stimulating factor (G-CSF) to the subject.

9. A combination therapy comprising a CD11c agonist selected from selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a- heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, and a G-CSF.

10. The combination therapy of claim 9, wherein the CD11c agonist and the G-CSF are formulated together or separately.

11. A pharmaceutical composition comprising a CD11c agonist selected from selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy- 1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene- 4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, a G-CSF, and a pharmaceutically acceptable excipient.

12. A kit comprising a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid;Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, or a pharmaceutical composition thereof, and instructions for using the CD11c agonist or the pharmaceutical composition in the method of any of claims 1-8.

13. A method of enhancing neutrophil maturation, the method comprising contacting a neutrophil with a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, thereby enhancing neutrophil maturation.Attorney Docket No.167705-035801 / PCT Electronic Deposit Date: May 29, 2025 14. A method of enhancing neutrophil function, the method comprising contacting a neutrophil with a CD11c agonist selected from the group consisting of (1S,2R,4As,6aR,6aS,6bR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl- 2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid; (Z)-3-(1,3-Benzodioxol-5-yl)-1-(4-fluorophenyl)prop-2-en-1-one; 10074-G5; 4a Phorbol 1213- didecanoate; 5-(N-ethyl-N-isopropyl)-Amiloride; 5-R-Rivaroxaban; 6-[[3- (aminomethyl)phenyl]methoxy]-7H-purin-2-amine; Atosiban; AZD1152-HQPA; Bosentan; BS- 181; Calcipotriol; CB-839; Cetrorelix Differine; CD-271; Differin; Adapalene; CD-0271; D01112; Differin Xp; Tactupump; ADAPALENE; adapalenum; Differin - Gel Top 0.1%; adapalene; Adapalenum; Differin - Liq Top 0.1%; Adaferin; 6-(3-(1-Adamantyl)-4- methoxyphenyl)-2-naphthoic acid; Epiduo Forte; Epiduo; Adapaleno; Eltrombopag; GR 55562 dihydrochloride; Imatinib metabolite N-Desmethyl Imatinib; n-Demethylated piperazine; CGP- 74588; F-0193; N-desmethylimatinib; Isradipine; MBX-2982; MK2-IN-1 (hydrochloride); ML 299; ML-298; mL347; Obatoclax; OSU-03012; PG-01; SN-38; NeoLipid; Camptosar; HCPT; Liposome entrapped SN38; LE-SN38; 7-Ethyl-10-Hydroxy-Camptothecin; EHC; Liposome entrapped 7-ethyl-10-hydroxycamptothecin; 7-ETHYL-10-HYDROXY-CAMPTOTHECIN; SP- 50; STK155799; STK810090; TAK-285; TAK-779; TC HSD 21; Testolactone; Torcetrapib; and UNC2250, thereby enhancing neutrophil function.

15. The method of claim 13 or claim 14, wherein the method is conducted in vivo, ex vivo, or in vitro.

16. The method of claim 15, wherein the method is conducted in vivo in a subject, and the subject has a bacterial infection and / or sepsis.