Application of YBX1 in regulating macrophages in mycobacterium tuberculosis infection

Abstract

The invention discloses application of YBX1 in regulating macrophages in mycobacterium tuberculosis infection, relates to the technical field of biological medicines, and has the technical key points that the YBX1 has a regulating effect on macrophage autophagy induced by mycobacterium tuberculosis, and promotes generation of autophagy flow in the macrophages after mycobacterium tuberculosis infection. According to the present invention, the autophagy phenomenon in the TB is verified, the strong correlation between the expression of the YBX1 and the autophagy factor is determined, the YBX1 is the potential regulatory factor of the cell autophagy caused by M.tb infection, the downstream target gene of the YBX1 is preliminarily predicted by combining the bioinformatics analysis, and the regulation effect of the YBX1 on the BCG-induced macrophage autophagy has been preliminarily verified; the effect of YBX1 on resisting M.tb of mice is verified from the in-vivo level by successfully utilizing small interfering RNA (Ribonucleic Acid).

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to application of YBX1 in regulating macrophages during Mycobacterium tuberculosis infection. Background Art

[0002] Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M.tb) infection that can accumulate in multiple organs, among which pulmonary tuberculosis is the most common. In recent years, the increasing number of multidrug-resistant tuberculosis strains and M.tb / HIV co-infection has put TB prevention, control and treatment under tremendous pressure and severe challenges. Therefore, it is one of the research focuses at home and abroad to clarify the etiology of TB from the perspective of the host and to discover drug targets. It is reported that after M.tb invades the body, macrophages phagocytize pathogens and kill the invading pathogens through programmed death such as apoptosis and autophagy. M.tb has also evolved a variety of means to evade immunity and continue to survive latently in granulomas. The result of the interaction between the two determines the patient's health status: successful immunity or disease.

[0003] At present, there is still a lack of targeted therapeutic drugs for the diagnosis and treatment of TB in clinical practice. It is very important to study new potential targets based on the programmed cell death of macrophages. Therefore, clarifying the pathogenesis of M.tb after infection of macrophages requires a lot of basic research, which is of great significance for finding new therapeutic targets. Summary of the invention

[0004] The purpose of the present invention is to solve the above problems and provide the use of YBX1 in regulating macrophages in Mycobacterium tuberculosis infection.

[0005] In order to achieve the above object, the technical solution of the present invention is as follows:

[0006] The present invention provides the use of YBX1 for regulating macrophages in Mycobacterium tuberculosis infection. YBX1 has a regulating effect on Mycobacterium tuberculosis-induced macrophage autophagy.

[0007] The present invention is further configured as follows: YBX1 promotes the occurrence of autophagic flux in macrophages after infection with Mycobacterium tuberculosis.

[0008] The present invention is further configured as follows: YBX1 reduces the expression of inflammatory factors and tissue fluid exudation in tissues after infection with Mycobacterium tuberculosis.

[0009] The present invention is further provided as follows: application of YBX1 in treating tuberculosis.

[0010] Compared with the prior art, the beneficial effects of this solution are as follows: it confirms the existence of autophagy in TB, clarifies that there is a strong correlation between the expression of YBX1 and autophagy factors, and that it is a potential regulatory factor for cellular autophagy caused by M.tb infection. Combined with bioinformatics analysis, the downstream target genes of YBX1 were preliminarily predicted, and it was found that the increased expression of YBX1 was positively correlated with the expression of the transcription factor PLEKHM1. Motif analysis predicts that there are specific binding sites for PLEKHM1 in the non-coding region of the YBX1 gene during BCG infection, and PLEKHM1 is closely related to cellular autophagy. At the same time, the present invention has preliminarily verified the regulatory effect of YBX1 on BCG-induced macrophage autophagy. Small interfering RNA was successfully used to verify the effect of YBX1 on mouse resistance to M.tb at the in vivo level. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 It is a technical roadmap for exploring the promotion of the occurrence and development of pulmonary tuberculosis by YBX1 in the embodiments of the present invention;

[0012] Figure 2 It is a technical roadmap of the regulatory effect and molecular mechanism of YBX1 regulating BCG-infected macrophages in the embodiment of the present invention;

[0013] Figure 3 It is a technical roadmap for exploring the mechanism of action of YBX1 on inflammatory response and autophagy in lung tissue of BCG-infected mice in the embodiments of the present invention;

[0014] Figure 4 is a diagram of the possible mechanism of YBX1 regulating macrophage autophagy after M.tb infection in the embodiment of the present invention;

[0015] Figure 5 1 is a survey and research diagram of the autophagy phenomenon in the transcriptome data of TB patients in the embodiment of the present invention, wherein A is a volcano diagram visually showing differentially expressed mRNA transcripts, B is a highly similar transcriptional profile feature between pulmonary tuberculosis patients and extrapulmonary tuberculosis patients, C is the expression of autophagy-related genes analyzed based on transcriptional data, D is the expression of YBX1 in pulmonary tuberculosis patients, and E and F are the correlations between YBX1 transcripts and autophagy-related factors;

[0016] Figure 6 It is a diagram showing the high expression of YBX1 in vivo after M.tb infects humans and mice in the embodiment of the present invention, wherein A is the high expression of YBX1 mRNA level in the peripheral blood of tuberculosis patients, B and C are the high expression of YBX1 protein level in human lung tissue, and DF are the high expression of YBX1 protein level and mRNA level in the lung tissue of BCG-infected mice;

[0017] Figure 71 is a graph showing the effect of interfering with YBX1 on bacterial load and inflammatory infiltration in the lung tissue of mice infected with BCG in an embodiment of the present invention, wherein AB is YBX1 small interfering RNA, CD is the expression of YBX1 after interfering with YBX1 and combined with BCG infection detected by Western blot, E is HE staining observation showing that the level of inflammation in the lung tissue of mice after interfering with YBX1 combined with BCG infection increased, and F is plate spread culture showing that interfering with YBX1 combined with BCG infection;

[0018] Figure 8 1 is a diagram of the regulatory effect of YBX1 on BCG-induced macrophage autophagy in an embodiment of the present invention, wherein A shows that the survival rate of macrophages decreases with the increase of BCG infection concentration, BD shows that the expression levels of YBX1 protein and autophagy-related protein LC3 are significantly upregulated at 12 hours of infection, and E shows that after knocking down YBX1, the accumulation of autophagosomes (red highlights) and autophagic lysosomes (yellow highlights) in BCG-infected macrophages is significantly reduced, indicating that YBX1 can promote the occurrence of autophagic flow in macrophages after BCG infection;

[0019] Fig. 9 It is a target gene prediction diagram of the YBX1 transcription factor in the embodiment of the present invention. The increased expression of YBX1 is positively correlated with the expression of the transcription factor PLEKHM1, and PLEKHM1 is closely related to cellular autophagy. Among them, AB obtains the YBX1 transcription factor motif binding site based on the JASPAR 2024 database, evaluates the potential regulation according to whether the transcription factor binding site falls in the promoter region, and then screens 8720 potential target genes. CD selects YBX1-related ChIP experimental results from the ENCODE database, and screens 1085 potential target genes with YBX1 as the key node. EF analyzes the target genes potentially related to YBX1 expression based on the RNA expression data in GSE107994. DETAILED DESCRIPTION

[0020] In order to enable those skilled in the art to better understand the solution of the present invention, the technical solution of the present invention will be further described in detail below in conjunction with the embodiments of the present invention and the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0021] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments of the present invention can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.

[0022] Research content

[0023] (1) Study the important role of YBX1 in promoting the occurrence and development of pulmonary tuberculosis

[0024] The RNA-seq dataset GSE107994 of peripheral blood samples with TB characteristics in the GEO database was screened to analyze the differential expression of transcripts of cytokines related to the autophagy pathway in peripheral blood and their correlation with YBX1 expression; previously, we cooperated with the Fourth People's Hospital of Ningxia to carry out research on TB treatment, prevention and pathogenic mechanism. We have collected more than 200 peripheral blood samples from active TB patients and healthy people, extracted total RNA from the blood and obtained cDNA samples through reverse transcription, and used real-time fluorescence quantitative PCR technology to detect and analyze the expression of YBX1 in active TB patients and healthy people. The expression differences in the peripheral blood of different groups of people; studied and verified that YBX1 promotes BCG-induced macrophage autophagy at the cell line level: constructed different mononuclear macrophage cell lines with YBX1 knockdown and overexpression, detected the expression changes of YBX1 after BCG infection at different times / different multiplicity, and clarified that YBX1 is involved in the immune regulation process during M.tb infection; constructed the time gradient and concentration gradient models of BCG-infected C57BL / 6J wild-type mice, and detected the expression of YBX1 in mouse serum and lung tissue by protein immunoblotting technology and real-time fluorescence quantitative PCR technology.

[0025] (2) Regulatory effect of YBX1 on macrophage autophagy after M.tb infection

[0026] Different mononuclear macrophage cell lines with YBX1 knockdown and overexpression were constructed, and macrophage proliferation was detected by CCK8. Transmission electron microscopy, flow cytometry and other methods were used to detect the number of cellular autophagosomes, the fusion of autophagosomes and lysosomes, and the level of autophagic flux. The key stage through which YBX1 regulates M.tb-induced macrophage autophagy was clarified, and the relevant activators / inhibitors of this stage were further used for verification to clarify the regulatory effect of YBX1 on macrophage autophagy.

[0027] 18-22g C57BL / 6N female mice were selected and airway instillation blank control group, airway instillation siRNA group, airway instillation BCG group, and airway instillation BCG+siRNA group were set up; the mice were killed on the 29th day and the mouse lungs were obtained. Immunohistochemistry, flow cytometry, immunofluorescence, real-time fluorescence quantitative PCR and protein immunoblotting techniques were used to detect the expression of autophagy-related proteins in the lung tissue of mice, lung tissue damage, changes in bacterial load in the lung tissue of mice, expression of inflammatory factors in the blood, and recruitment of immune cells in the lung tissue, to clarify the effect of knocking out YBX1 on the changes in tissue-level inflammation and changes in autophagy-related factors and pathways after BCG infection.

[0028] Study plan

[0029] (1) Based on the correlation analysis between autophagy and YBX1 in peripheral blood transcriptome of TB patients, the difference in YBX1 expression after M.tb infection was clarified

[0030] ① Based on the GSE107994 dataset selected from the clinical medicine public database GEO, peripheral blood mRNA transcriptome data from three groups of people, including healthy people of different races, genders, and ages, pulmonary tuberculosis patients, and extrapulmonary tuberculosis patients, were selected as research objects. The selected samples were grouped and normalized using the chip / transcriptome online analysis tool GEOR2 provided by GEO. When performing statistical analysis of sample transcript differences, GO and KEGG enrichment analysis of peripheral blood transcriptome data of TB patients was performed.

[0031] ②Analysis of autophagy differences in peripheral blood of TB patients: One-way ANOVA and Tukey method were used to statistically analyze the differences in transcriptional expression levels of autophagy-related factors in the peripheral blood of healthy people, pulmonary tuberculosis patients and extrapulmonary tuberculosis patients using GEO samples that were screened and qualified. Further, the correlation matrix was drawn based on the expression values ​​of transcript screening data and laboratory data to analyze the correlation between differentially expressed autophagy signaling pathway factors and YBX1 transcripts in the peripheral blood of TB patients.

[0032] ③Peripheral blood samples were collected from active TB patients and healthy subjects, and total RNA in cells was extracted using the Trizol method. The RNA quality was determined using Nanodrop 2000 (Thermo Scientific, USA), and the RNA integrity was detected using 1.3% agarose gel electrophoresis (120V, 15min, 1×FAbuffer). Total RNA (2.5μg) was incubated with 10U RNase R (Gisai Company, China) at 37℃ for 30min. RT reagent Kit was used to perform reverse transcription experiment on RNA to obtain cDNA, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression difference of YBX1 before and after infection.

[0033] ④ Collect lung tissue samples from active TB patients and healthy subjects, and use immunohistochemistry and protein immunoblotting techniques to detect the expression difference of YBX1 in the lung tissues of TB patients and healthy subjects, respectively.

[0034] ⑤ C57BL / 6J mice (6-8 weeks old) were used as the research model, and adaptive culture was performed for 1 week to eliminate experimental errors caused by differences in the culture environment. BCG (1×105CFU / mouse) was infected by airway perfusion, with 6-8 mice in each group. The phenotypic changes of mouse lung tissue were observed at different infection periods (1 day, 6 days, 14 days and 28 days). The weight change coefficient = the mean weight of the time group / the mean weight of the 0-day weight. The changes in the dry-wet specific gravity of the lung tissue (the ratio of wet weight / dry weight of the left lung of the mouse) were measured by weighing. On the 21st day, peripheral blood of the mouse was obtained by orbital bleeding. The mouse was killed by cervical dislocation. A 0.4 cm2 tissue block of the mouse lung was taken and immersed in 1 mL of 4% paraformaldehyde fixative for the preparation of paraffin sections. HE staining was used to evaluate the structural integrity and inflammatory infiltration of the lung tissue. Immunohistochemistry, protein immunoblotting and immunofluorescence were used to detect the expression changes of YBX1 in lung tissue.

[0035] ⑥ Use BCG to infect macrophages (MOI=10), and at different times after infection (0h, 6h, 12h, 18h and 24h), use real-time fluorescence quantitative PCR and protein immunoblotting technology to detect the expression of YBX1 and autophagy marker protein LC3Ⅱ, so as to clarify the effect of M.tb infection on the expression of YBX1 in macrophages and the potential relationship between YBX1 and cellular autophagy.

[0036] (2) Regulatory effect of YBX1 on macrophage autophagy after M.tb infection

[0037] ① Isolate and culture bone marrow macrophages (BMDM) from C57BL / 6J mice. After 7 days of culture, stain them with macrophage surface marker antibodies (CD11b and F4 / 80). Detect the antibody positivity rate using flow cytometry to identify the successful induction of BMDM cells.

[0038] ② Observe the morphology and accumulation of autophagosomes and autolysosomes in macrophages by transmission electron microscopy. Combined with autophagosome-specific dyes The cells were stained with Autophagy Detection Kit 2.0, and the fluorescence intensity was detected by flow cytometry to monitor the autophagy rate of the cells.

[0039] ③The co-localization of autophagosome membrane protein LC3 and lysosome surface protein LAMP2 in macrophages was observed by fluorescence microscopy to evaluate the fusion of autophagosomes and lysosomes.

[0040] ④ Use the mCherry-GFP-LC3 dual fluorescence indicator system to monitor the autophagic flow in macrophages.

[0041] ⑤ Use fluorescence quantitative PCR and protein immunoblotting techniques to detect the expression of intracellular proteins involved in inducing autophagy (mTORC1, AMPK and ULK1, etc.) and proteins involved in autophagosome membrane formation (ATG5, ATG7 and LC3II / I, etc.), to clarify that YBX1 is mainly involved in regulating the key stages of macrophage autophagy.

[0042] ⑥ Treat the YBX1 knockout cell line with relevant signal pathway activators / inhibitors, and combine it with BCG infection. Use immunofluorescence technology, flow cytometry, real-time fluorescence quantitative PCR and protein immunoblotting to detect indicators such as cell autophagy rate, protein and nucleic acid expression of autophagy-related factors, and explore the regulatory role of YBX1 in M.tb-induced macrophage autophagy.

[0043] (3) Study on the role of YBX1 in mice's resistance to M.tb infection

[0044] ① 18-22g C57BL / 6N female mice were selected and cultured for 1 week to eliminate experimental errors caused by differences in the culture environment. Airway perfusion blank control group, airway perfusion siRNA group, airway perfusion BCG group, and airway perfusion BCG+siRNA group were set up. A saline control group and a BCG infection experimental group were set up separately, with 6-8 mice in each group.

[0045] ② Collect mouse lung tissue for morphological observation, and weigh and measure the changes in the dry-wet specific gravity of the lung tissue (the ratio of wet weight / dry weight of the left lung of the mouse).

[0046] ③ Prepare paraffin sections and use HE staining technology to evaluate the pathological damage of mouse lung tissue.

[0047] ④ Collect and grind the mouse lung tissue, spread it on Middlebrook 7H10 solid culture medium after gradient dilution, count the growth colonies of M.tb after 21 days, and finally calculate the bacterial load of the mouse lung tissue.

[0048] ⑤Collect peripheral blood of mice and extract serum, and use ELISA to detect the expression of inflammatory factors such as IL-6, TNF-α and IFN-γ in mouse serum and bronchoalveolar lavage fluid.

[0049] ⑥The recruitment of immune cells (macrophages, lymphocytes and neutrophils) in the bronchoalveolar lavage fluid of mice was detected by flow cytometry and cytology.

[0050] ⑦Use immunohistochemistry, immunofluorescence, real-time fluorescence quantitative PCR and protein immunoblotting techniques to detect the expression of autophagy-related proteins in mouse lung tissue and clarify the effect of YBX1 on M.tb infection-induced autophagy in mouse lung tissue.

[0051] (4) Study on the molecular mechanism of YBX1 regulating M.tb infection-induced macrophage autophagy

[0052] ① Enrichment screening and identification of YBX1 target genes: BCG was used to infect macrophages, and the fixative was added to the culture dish at a ratio of 1:10. The fixed cells were rinsed with 4℃ PBS, and then the lysis solution was added to fully resuspend. The cell lysis solution was ultrasonically broken to break the DNA (10×30s pulses, 5min in total, 18-21W), and the supernatant was obtained by centrifugation after ultrasonication. The corresponding antibody was added to the supernatant, incubated at 4℃ overnight, and 30μl proteinA / G Beads were added and incubated at 4℃ for 2 hours. After a series of gentle washings, the final beads were eluted with 250μl of the configured elution buffer, inverted at room temperature for 15min, and the supernatant was collected after static centrifugation. 20μl 5M NaCl (final NaCl concentration was 0.2M) was added to each tube to dissolve the cross-linking and mix well, and the cross-linking was dissolved at 65℃ overnight. DNA was purified after incubation with RNAaseA and proteinase K. The extracted DNA is subsequently used for library construction before being sequenced on the machine according to the specific requirements of DNA sequencing, and then the ChIP result changes of the corresponding samples are analyzed by bioinformatics.

[0053] ② Through sequencing technology and bioinformatics annotation, the downstream genes regulated by the target sequence were identified, and autophagy-related genes were screened to determine the target genes that YBX1 may regulate in the process of BCG-induced macrophage autophagy.

[0054] ③ Use BCG to infect macrophages, verify the interaction between YBX1 and the target sequence through CHIP technology, and further verify the expression differences of the predicted target genes through qPCR and other technologies.

[0055] ④ According to the target sequence, a dual luciferin reporter enzyme system was synthesized and co-transfected into 293T cells together with the YBX1 plasmid to clarify the interaction between YBX1 and the target sequence and its regulatory effect on the target gene.

[0056] Experimental data

[0057] (1) Analysis of YBX1 expression and autophagy based on peripheral blood transcriptome of TB patients, such as Figure 5 Shown

[0058] ① The volcano plot visualizes the differentially expressed mRNA transcripts. Compared with healthy people, pulmonary tuberculosis showed 4807 upregulated genes and 3496 downregulated genes; extrapulmonary tuberculosis showed 3995 upregulated genes and 2397 downregulated genes ( Figure 5 A);

[0059] ② Functional enrichment analysis of differentially expressed transcripts was performed in the GO database. The results showed that patients with pulmonary tuberculosis and patients with extrapulmonary tuberculosis showed highly similar transcriptional profiles, which were mainly enriched in biological processes such as activation of innate immune cells, regulation of innate immune responses, and resistance to intracellular bacterial infection ( Figure 5 B);

[0060] ③ The expression of autophagy-related genes was analyzed based on transcriptional data. The results showed that autophagy-related genes such as mTOR, ULK1, Beclin1, ATG5, ATG7 and LC3 were differentially expressed in patients with pulmonary tuberculosis, while some autophagy-related genes had no significant differences in patients with extrapulmonary tuberculosis, indicating that autophagy exists in active pulmonary tuberculosis ( Figure 5 C);

[0061] ④The differential transcript analysis of YBX1 revealed that the expression of YBX1 in patients with pulmonary tuberculosis was significantly upregulated compared with that in healthy subjects ( Figure 5 D)

[0062] ⑤ Compared with healthy subjects, in the data of 43 tuberculosis patients, YBX1 transcripts showed a high correlation with autophagy-related factors ( Figure 5 EF).

[0063] (2) Analysis of differential expression of YBX1 after M.tb infection

[0064] YBX1 in peripheral blood of TB patients ( Figure 6 A) Lung tissue of TB patients ( Figure 6 BC), BCG-infected mouse lung tissue and mouse serum ( Figure 6 DF), indicating that YBX1 may be involved in the immune regulation process during M.tb infection.

[0065] (3) Interference with YBX1 promotes bacterial load and inflammatory infiltration in lung tissue after BCG infection

[0066] Due to the lethal nature of the YBX1 gene knockout, previous experiments constructed synthetic YBX1 si-RNA and interfered with YBX1 expression in mouse lung tissue by airway perfusion, in order to preliminarily explore the in vivo biological effects of YBX1 after M.tb infection.

[0067] ①Compared with the NC transfection group, the interference effect of small interfering RNA No. 2 was the best (about 50%), significantly down-regulating the relative expression level of YBX1 protein ( Figure 7 AB);

[0068] ② After BCG infection, siRNA No. 2 can inhibit the upregulation of YBX1 in macrophages caused by BCG infection. Therefore, subsequent experiments used siRNA No. 2 as an interference tool for YBX1 ( Figure 7 CD).

[0069] ③HE staining results showed that after interfering with YBX1, the lung tissue of mice infected with BCG showed more obvious inflammatory cell infiltration, tissue fluid exudation and other damage phenomena, and the dry-wet ratio of the lung tissue of mice increased ( Figure 7 E).

[0070] ④ The results of plate coating showed that compared with the airway instillation BCG group, the BCG colonies formed in the 7H10 agar plate of mice in the si-YBX1 combined with airway instillation BCG group increased significantly. This suggests that the loss of YBX1 is beneficial to the survival of BCG in the lung tissue of mice ( Figure 7 F).

[0071] (4) YBX1 promotes M.tb infection-induced macrophage autophagy

[0072] ① The attenuated strain of Mycobacterium bovis, BCG (BCG), was selected as the test strain. Different infection multiplicity and infection time were designed. It was found that the survival rate of macrophages decreased with the increase of BCG infection concentration, and the expression levels of YBX1 protein and autophagy-related protein LC3 were significantly upregulated at 12h of infection ( Figure 8 AD);

[0073] ②Using mRFP-GFP-LC3 tandem fluorescent protein adenovirus to infect cells, the autophagic flow of cells can be evaluated intuitively and clearly by observing the number of yellow and red bright spots in the cells. The results showed that after knocking out YBX1, the accumulation of autophagosomes (red bright spots) and autophagic lysosomes (yellow bright spots) in BCG-infected macrophages was significantly reduced, indicating that YBX1 can promote the occurrence of autophagic flow in macrophages after BCG infection ( Figure 8 EF).

[0074] (5) Screening of target genes that may be regulated by YBX1

[0075] ① Based on the JASPAR 2024 database, the YBX1 transcription factor motif binding sites were obtained, and the potential regulation was evaluated according to whether the transcription factor binding sites fell in the promoter region, and then 8720 potential target genes were screened ( Fig. 9 AB);

[0076] ②Selected YBX1-related ChIP experimental results from the ENCODE database, and screened 1085 potential target genes with YBX1 as the key node ( Fig. 9 CD);

[0077] ③Based on the RNA expression data in GSE107994, target genes potentially related to YBX1 expression were analyzed. Combining the three results, it was found that after BCG infection, the increased expression of YBX1 was positively correlated with the expression of transcription factor PLEKHM1, and PLEKHM1 was closely related to cellular autophagy ( Fig. 9 EF).

[0078] The above specific embodiments are merely explanations of the present invention and are not limitations of the present invention. After reading this specification, those skilled in the art may make modifications to the embodiments without any creative contribution as needed. However, such modifications are protected by the patent law as long as they are within the scope of the claims of the present invention.

Claims

1. The application of YBX1 in regulating macrophages in Mycobacterium tuberculosis infection is characterized by: YBX1 regulates Mycobacterium tuberculosis-induced macrophage autophagy.

2. The use of YBX1 in regulating macrophages in Mycobacterium tuberculosis infection according to claim 1, characterized in that: YBX1 promotes autophagic flux in macrophages after Mycobacterium tuberculosis infection.

3. The use of YBX1 in regulating macrophages in Mycobacterium tuberculosis infection according to claim 1, characterized in that: YBX1 reduces the expression of inflammatory factors and tissue fluid exudation in tissues after Mycobacterium tuberculosis infection.

4. The use of YBX1 in regulating macrophages in Mycobacterium tuberculosis infection according to claim 1, characterized in that: Application of YBX1 in the treatment of tuberculosis.

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