Immunostimulant composition

Abstract

The purpose of the present invention is to provide a novel immunostimulating composition. The present invention provides an immunostimulating composition containing a lactic acid bacterium as an active ingredient. According to the present invention, the lactic acid bacterium, which is the active ingredient, can induce the production of IFN through the activation of pDC. Thus, the composition is advantageous in being usable as a functional food, a drug, etc. that imparts immunostimulatory effects, and also being usable as a functional food, a drug, etc. that is safe for mammals including humans. In particular, the composition of the present invention is advantageous in terms of being daily ingestible as a food and being able to easily achieve immunostimulation.

Description

Reference to related applications

[0001] This application enjoys priority from the preceding Japanese application, Japanese Patent Application No. 2023-44941 (filed on March 22, 2023), the entirety of which disclosure is incorporated herein by reference. [Technical Field]

[0002] This invention relates to an immunostimulatory composition. [Background technology]

[0003] The innate immune system is primarily responsible for the primary response to bacterial or viral infections, and dendritic cells are among its most powerful and important constituent cells. Plasmacytoid dendritic cells (pDCs) are major producers of various interferons (IFNs), including type I interferon (IFN), which exhibits inhibitory activity against viral proliferation, and thus play a crucial role in antiviral defense. Lactobacillus garvieae and Lactococcus lactis subspecies cremoris are known to activate pDCs with these characteristics (Patent Document 1). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication No. 2012 / 91081 [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] The present invention aims to provide a novel immunostimulatory composition. [Means for solving the problem]

[0006] The present invention provides the following inventions. [1] An immunostimulatory composition or immunostimulator comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, and Lactobacillus. [2] The composition or agent according to [1] above, wherein the genus Oenococcus is Oenococcus oeni, the genus Bifidobacterium is Bifidobacterium animalis subspecies lactis or Bifidobacterium longum subspecies infantis, the genus Lentilactobacillus is Lentilactobacillus parakefilii, the genus Weissella is Weissella paramesenteroides or Weissella viridesens, the genus Tetragenococcus is Tetragenococcus halophilus, the genus Lactococcus is Lactococcus plantarum, the genus Leuconostoc is Leuconostoc carnosum, and the genus Lactobacillus is Lactobacillus gasseri or Lactobacillus plantarum. [3] Oenococcus oeni is Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis is Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis is Bifidobacterium longum subspecies infantis JCM1222, Lentractobacillus paracephyli is Lentractobacillus paracephyli JCM8573, and Weissella paramesenteroides is Weissella paramesenteroides The composition or agent described in [2] above, wherein JCM9890 is Wysella viridescens, Wysella viridescens JCM1174, Tetragenococcus halophilus is Tetragenococcus halophilus NRIC0098, Lactococcus plantarum is Lactococcus plantarum JCM11056, Leuconostoc carnosum is Leuconostoc carnosum JCM9695, Lactobacillus gasseri is Lactobacillus gasseri SBT2055, and Lactobacillus plantarum is Lactobacillus plantarum L-137. [4] A composition or agent for the prevention or treatment of cold-like symptoms, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, and Lactobacillus. [5] A composition or agent for the prevention or treatment of viral infection, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, and Lactobacillus. [6] A composition or agent for activating plasmacytoid dendritic cells, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, and Lactobacillus. [7] A composition or agent for promoting interferon production, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, and Lactobacillus. [8] Use of lactic acid bacteria for the manufacture of immunostimulants, preventive or therapeutic agents for cold-like symptoms, preventive or therapeutic agents for viral infections, plasmacytoid dendritic cell activators, or interferon production promoters. [9] Use of lactic acid bacteria as an immunostimulant, a preventive or therapeutic agent for cold-like symptoms, a preventive or therapeutic agent for viral infections, a plasmacytoid dendritic cell activator, or an interferon production promoter.

[10] Use of lactic acid bacteria in immunostimulatory methods, methods for preventing or treating cold-like symptoms, methods for preventing or treating viral infections, methods for activating plasmacytoid dendritic cells, or methods for promoting interferon production.

[11] Lactobacillus for immune activation, prevention or treatment of cold-like symptoms, prevention or treatment of viral infections, plasmacytoid dendritic cell activation or promotion of interferon production.

[12] An immunostimulatory method, a method for preventing or treating cold-like symptoms, a method for preventing or treating viral infection, a method for activating plasmacytoid dendritic cells, or a method for promoting interferon production, comprising administering an effective amount of lactic acid bacteria or a composition containing the same to a subject in need.

[13] An immunostimulatory composition or immunostimulator comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Enterococcus, Bacillus and Lactobacillus.

[14] A composition or agent for the prevention or treatment of cold-like symptoms, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Enterococcus, Bacillus, and Lactobacillus.

[15] A composition or agent for the prevention or treatment of viral infection, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Enterococcus, Bacillus and Lactobacillus.

[16] A composition or agent for activating plasmacytoid dendritic cells, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Enterococcus, Bacillus, and Lactobacillus.

[17] A composition or agent for promoting interferon production, which contains lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus bacteria, Bifidobacterium bacteria, Lentilactobacillus bacteria, Weissella bacteria, Tetragenococcus bacteria, Lactococcus bacteria, Leuconostoc bacteria, Pediococcus bacteria, Streptococcus bacteria, Enterococcus bacteria, Bacillus bacteria and Lactobacillus bacteria.

[0007] The compositions of the above [1], [4] to [7] and

[13] to

[17] may be referred to as "the compositions of the present invention" in this specification, and the agents of the above [1], [4] to [7] and

[13] to

[17] may be referred to as "the agents of the present invention" respectively.

[0008] According to the present invention, since lactic acid bacteria as an active ingredient can induce IFN production by activating pDC, it can be used as a functional food (including health functional foods such as foods with functional claims, foods for specified health uses or foods with nutritional functions) or a pharmaceutical product or the like that imparts an immunostimulatory effect, and is advantageous in that it can be used as a functional food or a pharmaceutical product or the like that is safe for mammals including humans. In particular, the composition or agent of the present invention can be taken daily as a food, and is advantageous in that immunostimulation can be easily achieved.

Brief Description of Drawings

[0009]

Figure 1A

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[0010] The composition or agent of the present invention contains lactic acid bacteria as an active ingredient.

[0011] The lactic acid bacteria that are the active ingredient of the present invention can activate pDCs and induce the production of at least one type of IFN. The lactic acid bacteria that are the active ingredient of the present invention can also promote the expression of activation markers such as CD80, CD86, or MHC class II in pDC activation.

[0012] The lactic acid bacteria that are the active ingredient of the present invention can induce the production of at least one type of interferon (IFN), such as Type I IFN, Type II IFN, or Type III IFN. Type I IFN refers to cytokines that are effective against viral infections, and includes, for example, IFN-α (including subtypes such as 1, 2, 4, 5, 6, 7, 8, 10, 13, 14, 16, 17, or 21) or IFN-β. Type II IFN includes IFN-γ, and Type III IFN includes IFN-λ. The lactic acid bacteria that are the active ingredient of the present invention preferably have the activity to induce the production of at least Type I IFN. When pDCs are activated by lactic acid bacteria, which are the active ingredient of the present invention, cellular protrusions characteristic of activated dendritic cells appear, inducing the production of Type I IFN and / or Type III IFN, and potentially also inducing the production of Type II IFN such as IFN-γ from NK cells and Th1 cells.

[0013] The IFN that can be induced by lactic acid bacteria, which is the active ingredient of the present invention, is not particularly limited as long as it belongs to any of Type I IFN, Type II IFN, or Type III IFN, but it is preferable that it contains one or more selected from the group consisting of IFN-α, IFN-β, and IFN-λ, more preferably that at least one of the IFNs is IFN-α, even more preferably that at least one of the IFNs is IFN-α and one or more selected from the group consisting of IFN-α, IFN-β, and IFN-λ, even more preferably that at least one of the IFNs is IFN-α and two or more selected from the group consisting of IFN-α, IFN-β, and IFN-λ, even more preferably that at least two of the two or more IFNs are IFN-α and IFN-β, and it is particularly preferable that it contains all three types: IFN-α, IFN-β, and IFN-λ.

[0014] The fact that the lactic acid bacteria, which are the active ingredient of the present invention, can directly activate pDCs and induce the production of at least one type of IFN can be confirmed, for example, by measuring the amount or concentration of IFN such as IFN-α or IFN-β produced in the culture system due to the activation of pDCs when lactic acid bacteria are cultured in the presence of pDCs induced from the bone marrow cells of mammals such as mice.

[0015] Specifically, as shown in the examples below, the IFN concentration can be confirmed by measuring it using the following procedure (i) to (iv). (i) De-erythrocyte-removed mouse bone marrow cells are placed in RPMI medium prepared to the following composition in a 1 × 10⁶ state. 6 Suspend the cells to a concentration of cells / mL to prepare a cell suspension. <Composition of culture medium> • 10% FBS by volume • 100 U / mL Penicillin / Streptomycin 1 mM sodium pyruvate 2.5mM HEPES ·1 mass% MEM NEAA 50 μM β-mercaptoethanol • 100 ng / mL Flt-3L (ii) Seed 1 mL of the prepared cell suspension into each cell and culture in a CO2 incubator at 37°C and 5% CO2 for 1 week to induce pDCs. (iii) Bone marrow cells containing induced pDCs, 2 × 10 5 Suspend the bacteria to a concentration of 1 mg / mL, seed 200 μL into each 96-well plate, and add 2 μL of lactic acid bacteria suspension adjusted to a concentration of 1 mg / mL in PBS to each plate. (iv) After 24 hours, collect the culture supernatant and measure the IFN-α concentration by ELISA using an IFN-α measurement kit.

[0016] The active ingredient of the present invention is a lactic acid bacterium with a final concentration of 10 μg / mL, and a pDC containing 100 ng / mL Flt3-L obtained by culturing the lactic acid bacterium, which is recovered from mouse bone marrow, in a cell culture medium containing 100 ng / mL Flt3-L for 7 days, with a final concentration of 2 × 10 5 The index can be expressed as the amount of IFN-α produced by co-culturing cells / mL of bone marrow cells for 24 hours, which is 30 pg / mL (preferably 50 pg / mL, more preferably 60 pg / mL, more preferably 70 pg / mL, 80 pg / mL, 90 pg / mL, 100 pg / mL, 150 pg / mL, even more preferably 200 pg / mL, 210 pg / mL, 220 pg / mL, 230 pg / mL, 240 pg / mL, 250 pg / mL, even more preferably 300 pg / mL, 400 pg / mL, 500 pg / mL, 600 pg / mL, 700 pg / mL, and particularly preferably 800 pg / mL) or more.

[0017] The lactic acid bacteria that are the active ingredient of the present invention are not particularly limited, but for example, Oenococcus ( Oenococcus ) Genus, Bifidobacterium ( Bifidobacterium ) Genus, Lenticularbacillus ( Lentilactobacillus ) genus, Weissera ( Weissella ) Genus, Tetragenococcus ( Tetragenococcus ) genus, Lactococcus ( Lactococcus ) genus, Leuconostoc ( Leuconostoc ) genus, Pediococcus ( Pediococcus ) genus, Streptococcus ( Streptococcus) genus, Enterococcus ( Enterococcus ) genus, Lactobacillus ( Lactobacillus ) Genus and Bacillus ( Bacillus Examples include lactic acid bacteria belonging to the genus ).

[0018] Furthermore, the Lactobacillus species in this invention includes bacteria that were classified under the Lactobacillus genus before the reclassification of the Lactobacillus genus. For example, with the reclassification of the Lactobacillus genus, newly classified acetylactobacillus ( Acetilactobacillus ) genus, Agrilactobacillus ( Agrilactobacillus ) Genus, Amyloractobacillus ( Amylolactobacillus ) genus, Apiractobacillus ( Apilactobacillus ) Genus, bombilactobacillus ( Bombilactobacillus ) Genus, Companilactobacillus ( Companilactobacillus ) genus, delagrioa ( Dellaglioa ) Genus, Fructilactobacillus ( Fructilactobacillus ) Genus, Furfrylactobacillus ( Furfurilactobacillus ) Genus, Horzapferia ( Holzapfelia ) Genus, Lacticacea bacillus ( Lacticaseibacillus ) Genus, Lactiplanchibacillus ( Lactiplantibacillus ) Genus, Lapidilactobacillus ( Lapidilactobacillus ) Genus, Lacticactobacillus ( Latilactobacillus ) Genus, Lenticularbacillus ( Lentilactobacillus ) Genus, Leviractobacillus ( Levilactobacillus ) Genus, Lydiractobacillus ( Ligilactobacillus ) Genus, Limosilactobacillus ( Limosilactobacillus ) Genus, Lycoryllicactobacillus ( Liquorilactobacillus ) genus, Loigolactobacillus ( Loigolactobacillus ) genus, Pararactobacillus ( Paralactobacillus ) Genus, Pouch Lactobacillus ( Paucilactobacillus ) Genus, Schleiferylactobacillus ( [[ID= ) Genus, Secundilactobacillus ( ​ Includes bacteria classified into genera such as )

[0019] Examples of the genus Oenococcus include Oenococcus oeni, shown in the lactic acid bacteria list in Figure 1A. ​ ​Examples include the following. Specific examples of the genus Oenococcus include Oenococcus oeni JCM6125.

[0020] Examples of Bifidobacterium species include Bifidobacterium animalis subspecies lactis, as shown in the lactic acid bacteria list in Figure 1B. ​ ​ subsp. ​ ) and Bifidobacterium longum subspecies infantis ( ​ ​ subsp. ​ Examples include the following.Specific examples of Bifidobacterium species include Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, and Bifidobacterium longum subspecies longum BB536.

[0021] Examples of Lentilactobacillus species include Lentilactobacillus parakefilii ( ​ Examples include ) and others. A specific example of a Lentilactobacillus species is Lentilactobacillus parakefiri JCM8573.

[0022] Examples of Weissella species include Weissella paramesenteroides, shown in the lactic acid bacteria list in Figure 1C. ​ ​ Examples include *Weissella* and *Weissella viridescens*. Specific examples of *Weissella* species include *Weissella paramesenteroides* JCM9890 and *Weissella viridescens* JCM1174.

[0023] Examples of Tetragenococcus species include Tetragenococcus halophilus, as shown in the lactic acid bacteria list in Figure 1D. ​ ​Examples include the following. Specific examples of Tetragenococcus species include Tetragenococcus halophilus NRIC0098 and Tetragenococcus halophilus No. 1.

[0024] Examples of Lactococcus species include Lactococcus lactis, shown in the lactic acid bacteria list in Figure 1E. ​ ​ ), Lactococcus lactis subspecies lactis ( ​ ​ subsp. ​ ), Lactococcus garbieae ( ​ ​ ), Lactococcus lactis subspecies cremoris ( ​ ​ subsp. ​ ), Lactococcus lactis subspecies 'Holdniae' ( ​ ​ subsp. ​ ) and Lactococcus plantarum ( ​ ​ Examples include:

[0025] Specific examples of Lactococcus species include Lactococcus lactis subspecies lactis JCM5805, Lactococcus lactis subspecies lactis NBRC12007, Lactococcus lactis subspecies lactis NRIC1150, Lactococcus lactis subspecies lactis JCM20101, Lactococcus lactis subspecies lactis JCM7638, and Lactococcus lactis subspecies. Examples include Lactosus lactis ATCC11454, Lactococcus garvieae NBRC100934, Lactococcus lactis subspecies cremoris JCM16167, Lactococcus lactis subspecies cremoris NBRC100676, Lactococcus lactis subspecies heldniae JCM1180, Lactococcus lactis subspecies heldniae JCM11040, and Lactococcus plantarum JCM11056.

[0026] Examples of Leuconostoc species include Leuconostoc carnosum, shown in the lactic acid bacteria list in Figure 1F. ​ ​ ) and Leuconostoc lactis ( ​ ​ Examples include the following. Specific examples of Leuconostoc species include Leuconostoc carnosum JCM9695 and Leuconostoc lactis NBRC12455.

[0027] Examples of Pediococcus species include Pediococcus acidilactici, as shown in the lactic acid bacteria list in Figure 1G. ​ ​ ), Pediococcus pentosaceus ( ​ pentosaceus ), Pediococcus cericola ( Pediococcus cellicola ), Pediococcus craussenii ( Pediococcus claussenii ), Pediococcus damnosus ( Pediococcus damnosus), Pediococcus etanoridurans ( Pediococcus ethanolidurans ), Pediococcus inopinatus ( Pediococcus inopinatus ), Pediococcus parvulus ( Pediococcus parvulus ), Pediococcus stilesii ( Pediococcus styles Examples include the following. Specific examples of Pediococcus species include Pediococcus acidilactici JCM8797, Pediococcus acidilactici K15, and Pediococcus damnosus JCM5886.

[0028] Examples of Streptococcus species include Streptococcus thermophilus, as shown in the lactic acid bacteria list in Figure 1H. Streptococcus thermophilus Examples include the following. Specific examples of Streptococcus species include, for instance, Streptococcus thermophilus SBC8781.

[0029] Examples of Enterococcus species include Enterococcus arcedinis, as shown in the lactic acid bacteria list in Figure 1I. Enterococcus alcedinis ) and Enterococcus faecalis ( Enterococcus faecalis Examples include Enterococcus faecalis EC-12.

[0030] Examples of Lactobacillus species include Lactobacillus paracasei, as shown in the lactic acid bacteria list in Figure 1J. Lactobacillus paracasei ), Lactobacillus delbruecki ( Lactobacillus delbrueckii ), Lactobacillus acidophilus ( Lactobacillus acidophilus ), Lactobacillus casei ( Lactobacillus households ), Lactobacillus fructivorance ( Lactobacillus fructivorans ), Lactobacillus hilgardii ( Lactobacillus hilgardii ), Lactobacillus rhamnosus ( Lactobacillus rhamnosus ), Lactobacillus plantarum ( Lactobacillus plantarum ), Lactobacillus gasseri ( Lactobacillus gasser ), Lactobacillus acidophilus ( Lactobacillus acidophilus ) and Lactobacillus bulgaricus ( Lactobacillus bulgaricus ) are some examples.

[0031] Specific examples of Lactobacillus species include Lactobacillus paracasei KW3110, Lactobacillus paracasei MCC1849, Lactobacillus paracasei K71, Lactobacillus paracasei K-2, Lactobacillus rhamnosus GG, Lactobacillus rhamnosus CRL1505, Lactobacillus gasseri SBT2055, and Lactobacillus plantarum (Lactiplantibacillus plantarum in the new classification) L-13. 7. Examples include Lactobacillus acidophilus L-92, Lactobacillus casei subspecies casei 327, Lactobacillus casei (Lacticaseibacillus paracasei in the new classification) Shirota, Lactobacillus parakephyli (Lentilactobacillus parakephyli in the new classification) JCM8573, and Lactobacillus pentosus (Lactiplanticbacillus pentosus in the new classification) ONRICb0240.

[0032] Examples of Bacillus species include Bacillus coagulans. Bacillus coagulans Examples include the following. Specific examples of Bacillus species include, for instance, Bacillus coagulans strain SANK70258.

[0033] In addition to the lactic acid bacteria mentioned above, the lactic acid bacteria shown in Figures 1A to 1J are further examples of the lactic acid bacteria that are the active ingredient of this invention.

[0034] Among the lactic acid bacteria that are the active ingredients of this invention, for example, the JCM strain can be obtained from the Microbial Materials Development Laboratory, BioResource Center, RIKEN (3-1-1 Takanodai, Tsukuba, Ibaraki Prefecture), the NBRC strain from the Biological Genetics Division, National Institute of Technology and Evaluation (2-5-8 Kazusa-Kamatari, Kisarazu, Chiba Prefecture), the NRIC strain from the Strain Preservation Room, Tokyo University of Agriculture (1-1-1 Sakuragaoka, Setagaya-ku, Tokyo), and the ATCC strain from the American Type Culture Collection (USA). In addition to obtaining the lactic acid bacteria that are the active ingredients of this invention from public institutions, they can also be obtained by isolating or purifying lactic acid bacteria from commercially available products containing lactic acid bacteria using known methods.

[0035] The lactic acid bacteria that are the active ingredient of the present invention may be a culture of lactic acid bacteria. The culture includes live cells, dead cells, crushed live or dead cells, freeze-dried live or dead cells, crushed freeze-dried products, enzyme-treated products of live or dead cells, culture solution or culture solution extract, and also includes a portion of lactic acid bacteria or treated products of lactic acid bacteria. Dead cells can be obtained from live cells by, for example, heat treatment, treatment with drugs such as antibiotics, treatment with chemical substances such as formalin, treatment with ultraviolet light or treatment with radiation such as gamma rays. Treated products include, for example, heated cells (dead cells), freeze-dried products thereof, and cultures containing these, and also include bacterial crushing solutions by ultrasound or the like, and enzyme-treated bacterial solutions. Furthermore, the treated products also include treated products from which the cell wall has been removed by enzymes or mechanical means. In addition, nucleic acid-containing fractions obtained by dissolving bacteria with a surfactant and then precipitating them with ethanol are also included. The lactic acid bacteria that are the active ingredient of the present invention also contain the DNA or RNA of the lactic acid bacteria in the culture. The DNA or RNA of the lactic acid bacteria can activate pDCs and induce IFN production.

[0036] Lactic acid bacteria can be cultured using known methods with known culture media. MRS medium, GAM medium, or LM17 medium can be used, and inorganic salts, vitamins, amino acids, antibiotics, and / or serum may be added as appropriate. Culturing can be carried out at 25-40°C for several hours to several days.

[0037] After culturing, the lactic acid bacteria can be collected from the resulting culture solution by centrifugation or filtration to obtain the desired lactic acid bacteria. When using dead lactic acid bacteria, they may be sterilized and inactivated by autoclaving or other methods before use.

[0038] The composition or agent of the present invention can enhance the immune activity of the body by activating pDCs in vivo and inducing the production of one or more IFNs, and therefore can be used for immunostimulation.

[0039] The composition or agent of the present invention may also contain materials other than lactic acid bacteria, which are the active ingredient, as components that can enhance immune activation. Such materials are not particularly limited as long as they can enhance immune activation, but examples include milk components (lactoferrin, etc.), green tea components (quercetin, catechin, caffeine, etc.), rosehip polyphenols, blackcurrant polyphenols, curcumin, turmeric, docosahexaenoic acid (DHA), astaxanthin, β-glucan, resveratrol, xanthophyll, milk ceramide, black tea polyphenols (BTP, etc.), lutein, phosphatidylserine, glycerophosphocholine, theaflavin, orotic acid, or yeast, etc. Materials that can be obtained by known methods such as reagents or commercially available products can be used.

[0040] While not particularly limited, examples of catechins include (+)-catechin, (-)-catechin, (-)-catechin 3-gallate, (-)-epicatechin, (-)-epicatechin-3-gallate, (-)-epigallocatechin 3-gallate, (-)-gallocatechin, or (-)-gallocatechin 3-gallate, and these can be used as reagents or commercially available products.

[0041] The composition or agent of the present invention is preferably used by oral administration from the viewpoint of reducing the burden of intake. When used by oral administration, the lactic acid bacteria or the composition or agent containing lactic acid bacteria is preferably highly resistant to gastric juice and intestinal juice, for example, has strong acid resistance. The lactic acid bacteria are not particularly limited, and both live and dead bacteria can be used, but dead bacteria are preferred from the viewpoint of immunostimulatory effect, stability and manufacturing efficiency, and heat-killed bacteria are more preferred.

[0042] Here, the lactic acid bacteria, which are the active ingredient of the present invention, can activate pDCs and induce the production of at least one type of IFN, and the IFN is not administered directly to the body. When IFN is administered directly to the body, it can be administered orally or parenterally. When IFN is administered orally directly to the body, it has poor resistance to gastric and intestinal juices, so degradation occurs and the possibility of it being absorbed into the body as IFN is low. Furthermore, when IFN is administered parenterally directly to the body, for example, subcutaneous administration is possible, but the burden of intake is high and the risk of side effects (fever, headache, depression, etc.) has been reported. Therefore, the lactic acid bacteria, which are the active ingredient of the present invention, can be said to be superior to the direct administration of IFN to the body because it can be taken orally, which reduces the burden of administration, the risk of side effects can be reduced, and an immunostimulatory effect equivalent to or greater than that of IFN can be obtained.

[0043] The composition or agent of the present invention can be provided in the form of a composition mixed with lactic acid bacteria and other components (e.g., food raw materials, food additives, pharmaceutical additives). The content of lactic acid bacteria in the composition can be determined based on the manner in which the composition or agent is provided and the effective intake amount described later, but the lower limit (greater than or equal to) can be, for example, 0.01% by mass, 0.1% by mass, 1% by mass, 10% by mass, or 20% by mass, and the upper limit (less than or equal to) can be, for example, 100% by mass, 90% by mass, 80% by mass, 70% by mass, 60% by mass, or 50% by mass. These lower and upper limits can be arbitrarily combined, and the content of lactic acid bacteria in the composition can be, for example, 0.01 to 100% by mass, 0.1 to 90% by mass, 10 to 80% by mass, or 20 to 70% by mass. The agent of the present invention can be provided as an immunostimulant containing lactic acid bacteria as an active ingredient.

[0044] The composition or agent of the present invention can be provided, for example, in the form of food, pharmaceuticals, quasi-drugs, animal feed (including pet food), or additives, and can be implemented according to the following description.

[0045] The composition or agent of the present invention can be administered orally to humans and non-human mammals, with food (e.g., food composition) being a typical form of administration. When the composition or agent of the present invention is provided as food, it may be provided as food as is, or it may be provided contained in food. The food provided is food containing an effective amount of the composition or agent of the present invention. Here, "containing an effective amount" means a content such that, when the amount normally consumed in each food is taken, the active ingredient of the present invention is taken in sufficient quantity to exert effects such as immune activation. Furthermore, "food" is used to include health foods, functional foods, nutritional supplements, health functional foods (e.g., Foods for Specified Health Uses, Nutritional Functional Foods, Foods with Function Claims), foods for special dietary uses (e.g., foods for infants, foods for pregnant and lactating women, foods for the sick), and supplements. Needless to say, when the active ingredient of the present invention is administered to mammals other than humans, the food referred to in the present invention is used as feed.

[0046] The composition or agent of the present invention has effects such as immune activation, and can therefore be provided by being included in foods consumed daily. In this case, the composition or agent of the present invention can be provided in a unit package form in which the amount to be consumed per serving is predetermined. Examples of unit package forms per serving include packs, packaging, cans, or bottles that specify a fixed amount. In order to better exert the various effects of the composition or agent of the present invention, the amount to be consumed per serving can be determined according to the daily intake amount of the active ingredient of the present invention, as described later. The food of the present invention may be provided with information regarding the amount to be consumed displayed on the packaging, or together with a document containing such information.

[0047] The predetermined intake amount per serving in the unit packaging form may be the effective daily intake amount, or it may be the effective daily intake amount divided into two or more (preferably two to six) doses. Therefore, the unit packaging form of the composition or agent of the present invention can contain the active ingredient of the present invention in the amount of the daily intake amount described below, or it can contain the active ingredient of the present invention in an amount of half or less (preferably half to one-sixth) of the daily intake amount described below. For convenience of intake, it is preferable to provide the composition or agent of the present invention in a unit packaging form per serving (i.e., a unit packaging form per day) in which the intake amount per serving is the effective daily intake amount.

[0048] The form of "food" is not particularly limited; for example, it may be in the form of a beverage, a semi-liquid or gel, a solid or powder. Examples of "supplements" include tablets manufactured by kneading the active ingredient of the present invention with excipients, binders, etc., and then compressing them into tablets; granules manufactured by granulating the active ingredient of the present invention with excipients, binders, etc.; orally disintegrating tablets; and capsules containing the active ingredient of the present invention enclosed in capsules, etc. When providing as a supplement, in addition to the above-mentioned per-serving or per-day unit packaging, it is also preferable to provide it in per-week, per-two-week, per-month, or per-two-month unit packaging. In the latter unit packaging, it is preferable to display, for example, the amount to be taken per serving or per day, so that the person taking the supplement can effectively ingest the active ingredient of the present invention according to that display.

[0049] The foods provided in this invention are not particularly limited as long as they contain the active ingredients of the invention, but examples include: soft drinks, carbonated drinks, fruit juice drinks, vegetable juice drinks, fruit and vegetable juice drinks, milk and other dairy products, soy milk, dairy beverages, drinkable yogurt, drinkable or stick-type jellies, coffee, cocoa, tea beverages, nutritional drinks, energy drinks, sports drinks, mineral water (including both sparkling and non-sparkling), near water, non-alcoholic beverages such as non-alcoholic beer-flavored beverages; carbohydrate-containing foods and beverages such as rice dishes, noodles, bread or pasta; cheeses, hard or soft yogurt, fresh cream made from dairy products or other oils and fats, ice cream. Examples include dairy products such as cream; Western-style confectionery such as cookies, cakes, and chocolates; Japanese-style confectionery such as manju or yokan; tablet candies such as ramune (refreshing candies); candies, gums, gummies, frozen desserts such as jelly or pudding, and various snack foods; alcoholic beverages such as whiskey, bourbon, spirits, liqueurs, wine, fruit wine, sake, Chinese liquor, shochu, beer, non-alcoholic beer with an alcohol content of 1% or less, sparkling wine, other miscellaneous alcoholic beverages, and chuhai; processed foods such as processed egg products, processed seafood or meat products (including offal such as liver) (including delicacies), and soups such as miso soup; seasonings such as miso, soy sauce, furikake, and other seasoning condiments; or liquid foods such as high-calorie liquid foods.

[0050] Tea beverages include fermented, semi-fermented, and unfermented teas, such as black tea, green tea, barley tea, brown rice tea, sencha, gyokuro tea, hojicha, oolong tea, turmeric tea, pu-erh tea, rooibos tea, rose tea, chrysanthemum tea, ginkgo leaf tea, and herbal teas (such as mint tea and jasmine tea).

[0051] Fruits used in fruit juice beverages and beverages containing both fruit and vegetable juices include, for example, apples, oranges, grapes, bananas, pears, peaches, mangoes, acai, blueberries, and plums. Vegetables used in vegetable juice beverages and beverages containing both fruit and vegetable juices include, for example, tomatoes, carrots, celery, pumpkins, cucumbers, and watermelons.

[0052] When providing the composition or agent of the present invention as animal feed, it can be carried out in accordance with the above description regarding food products.

[0053] When a composition or preparation is provided as a pharmaceutical product, quasi-drug, or pharmaceutical composition, it may be formulated as an oral or parenteral preparation. Examples of oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, liquids, jellies, emulsions, and suspensions. Examples of parenteral preparations include injectable preparations suitable for local administration (including intradermal, subcutaneous, intramuscular, and intravenous injections), inhalants (e.g., inhaled aerosols, inhaled powders, inhaled solutions), nasal drops (e.g., nasal powders, nasal solutions), ointments, creams, gels, suppositories, patches, and compresses. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly practiced in this art. Examples of pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, and preservatives.

[0054] When the composition or agent of the present invention is used as a pharmaceutical, quasi-drug, or pharmaceutical composition, the target diseases include, for example, cancers such as renal cancer, multiple myeloma, chronic myeloid leukemia, hairy cell leukemia, glioblastoma, medulloblastoma, astrocytoma, malignant melanoma, mycosis fungoides, and adult T-cell leukemia, which are already known to be indications for Type I IFN; viral infections such as subacute sclerosing panencephalitis, HTLV-1 myelopathy, hepatitis B, and hepatitis C; bacterial infections such as Chlamydia (sexually transmitted disease), Mycobacterium (tuberculosis), Listeria (sepsis, etc.), Staphylococcus (food poisoning), and Helicobacter (gastritis); and autoimmune diseases such as multiple sclerosis. The composition or agent of the present invention can be used for the prevention or treatment of the above diseases. Furthermore, since the activity of Type I IFN in the composition or agent of the present invention is known to be the inhibitory function of differentiation from osteoblasts to osteoclasts, it can also be used for the prevention or treatment of osteoporosis, etc.

[0055] The composition or agent of the present invention can be used as a vaccine by expressing or secreting antigens corresponding to specific diseases in or on the surface of lactic acid bacteria, which are the active ingredient, using genetic engineering techniques. In particular, because the cell wall of lactic acid bacteria protects antigens from stomach acid, heterologous antigen-expressing strains that express antigens in or on the surface of lactic acid bacteria are suitable as hosts for oral vaccines. Generally, vaccines include live vaccines, whole-particle inactivated vaccines, and split vaccines, but live vaccines carry the risk of viral virulence, whole-particle inactivated vaccines have concerns about side effects due to impurities, and split vaccines, which are considered the safest, are known to have problems with efficacy. By using the IFN-inducing lactic acid bacteria of the present invention as a recombinant vaccine that selectively expresses only the target antigen, an adjuvant effect can also be obtained, making it possible to use it as a pharmaceutical, quasi-drug, or pharmaceutical composition with extremely high utility and safety.

[0056] When providing the composition or agent of the present invention as an additive, it can be carried out according to the description regarding the above food, feed, pharmaceutical product, quasi-drug or pharmaceutical composition. When providing the composition or agent of the present invention as a food additive, the composition or agent of the present invention can be used as a functional ingredient involved in a food for specified health use or a food with functional claims having an immunostimulatory effect.

[0057] The intake amount of the composition or agent of the present invention can be determined depending on the sex, age and weight of the recipient, symptoms, intake time, dosage form, intake route, and materials or drugs to be combined, etc. The intake amount per day for an adult of the composition or agent of the present invention can be specified, for example, by the number of bacteria of lactic acid bacteria which is an active ingredient, and the lower limit value thereof can be 1×10 8 cells, 1×10 9 cells or 1×10 10 cells, and the upper limit value thereof can be 1×10 14 cells, 1×10 13 cells, 1×10 12 cells. These upper limit values and lower limit values can be arbitrarily combined respectively, and the range of the above intake amount can be, for example, 1×10 8 ~1×10 14 cells, 1×10 9 ~1×10 13 cells or 1×10 10 ~1×10 12 cells. The number of bacteria of lactic acid bacteria can be measured by a known microscope, flow cytometer or non-culture microorganism rapid inspection device (for example, ELESTA PixeeMo (AFI Technology Co., Ltd.)), etc., but measurement by a microscope is preferable from the viewpoint of high versatility.

[0058] The intake amount per day for an adult of the composition or agent of the present invention can also be specified by the dry cell mass of lactic acid bacteria which is an active ingredient, and the lower limit value thereof can be 2.5×10 -2 mg, 2.5×10 -1 mg or 2.5 mg, and the upper limit value thereof can be 2.5×10 4 mg, 2.5×10 3 mg, 2.5×10 2It can be expressed in mg. These upper and lower limits can be combined in any way, and the above intake range can be, for example, 2.5 × 10 -2 mg~2.5 × 10 4 mg, 2.5 × 10 -1 mg~2.5 × 10 3 mg, 2.5 mg ~ 2.5 × 10 2 It can be expressed as mg.

[0059] The above-mentioned dosage of the composition or agent of the present invention, as well as the timing and duration of intake described below, apply whether the composition or agent of the present invention is used for non-therapeutic or therapeutic purposes. In the present invention, "ingestion" and "administration" are interchangeable terms. It goes without saying that when the composition or agent of the present invention is used for non-therapeutic purposes, healthy individuals may be included among those taking the product.

[0060] Mammals, including humans, are targets for ingestion or administration of the composition or agent of the present invention. While there are no particular limitations on the mammals, examples include primates, rodents, carnivores, etc., with primates being preferred. Non-limiting examples of mammals include humans, chimpanzees, rhesus monkeys, marmosets, dogs, cats, cattle, horses, pigs, and sheep, with humans being preferred.

[0061] It is preferable to continue taking the composition or agent of the present invention for the duration during which an immunostimulatory effect is expected. From the viewpoint of better exhibiting the immunostimulatory effect, the period of intake of the active ingredient of the present invention can be, for example, one week or more, two weeks or more, three weeks or more, preferably one month or more (four weeks or more), based on the above daily dose. The interval between intakes of the active ingredient of the present invention can be once every three days, once every two days, or once a day, based on the above daily dose, and is preferably once a day.

[0062] The composition or agent of the present invention may also be taken before an event or time when an immunostimulatory effect is expected. Examples of events when an immunostimulatory effect is expected include activities that may lead to viral infection (e.g., participation in events with a high risk of viral infection, travel to an endemic area), and examples of times when an immunostimulatory effect is expected include the peak season for viral infection. Examples of timing for taking the agent before an event when an immunostimulatory effect is expected include, for example, one day or more before, three days or more before, one week or more before, two weeks or more before, three weeks or more before, one month or more before (four weeks or more before), or two months or more before (eight weeks or more before). Furthermore, although not particularly limited, the agent may be taken continuously with intervals between doses from the start of intake until the event when an immunostimulatory effect is expected. The active ingredient of the present invention may also be taken after an event or time when an immunostimulatory effect is expected. Examples of timing for taking the agent after an event when an immunostimulatory effect is expected include one day or more after, three days or more after, one week or more after, or two weeks or more after. Furthermore, although not limited thereto, when the active ingredient is taken after an event in which an immune-boosting effect is expected, it may be taken continuously with intervals between doses. In the present invention, it is particularly preferable to start taking the active ingredient of the present invention before an event in which an immune-boosting effect is expected, and to continue taking it until after the event.

[0063] The composition or agent of the present invention can also enhance the immune activity of the body by activating pDCs and inducing the production of one or more IFNs, and can therefore be used for the prevention or treatment of cold-like symptoms or viral infections.

[0064] In the present invention, "cold-like symptoms" refers to symptoms mainly caused by upper respiratory tract infections of pathogens (viruses, bacteria, etc.), and specific symptoms include, for example, cough, sore throat, sneezing, runny nose, nasal congestion, headache, fever, fatigue, and chills.

[0065] In the present invention, "viral infection" means that a living organism is infected with a virus, and examples of viruses include rhinovirus, coronavirus, influenza virus, adenovirus, parainfluenza virus, RSV, enterovirus, norovirus, rotavirus, herpesvirus, novel coronavirus (SARS-CoV-2), and measles virus.

[0066] When using the composition or agent of the present invention for the prevention or treatment of cold-like symptoms or for the prevention or treatment of viral infection, it can be carried out in the same manner as when using the composition or agent of the present invention for immunostimulation.

[0067] In another aspect of the present invention, a method for immunostimulation, a method for preventing or treating cold-like symptoms, a method for preventing or treating viral infections, a method for activating plasmacytoid dendritic cells, or a method for promoting interferon production is provided, comprising administering an effective amount of lactic acid bacteria or a composition or agent containing the same to a subject in need. The methods of the present invention can be carried out in accordance with the description relating to the composition or agent of the present invention.

[0068] Another aspect of the present invention also provides the use of lactic acid bacteria for the production of an immunostimulatory composition or immunostimulant, a composition or prophylactic agent for preventing or treating cold-like symptoms, a composition or prophylactic agent for preventing or treating viral infection, a prophylactic agent for treating viral infection, a composition or plasmacytoid dendritic cell activator, or an interferon production promoting composition or interferon production promoting agent.

[0069] Another aspect of the present invention also provides the use of lactic acid bacteria as an immunostimulatory composition or immunostimulant, a composition or preventive or therapeutic agent for cold-like symptoms, a composition or preventive or therapeutic agent for viral infection, a preventive or therapeutic agent for viral infection, a composition or plasmacytoid dendritic cell activator or plasmacytoid dendritic cell activator or an interferon production promoting composition or interferon production promoting agent.

[0070] Another aspect of the present invention also provides the use of lactic acid bacteria in an immunostimulatory method, a method for preventing or treating cold-like symptoms, a method for preventing or treating viral infections, a method for activating plasmacytoid dendritic cells, or a method for promoting interferon production.

[0071] The use of the present invention can be carried out in accordance with the description of the agent or method of the present invention.

[0072] In yet another aspect of the present invention, lactic acid bacteria are provided for immunostimulation, prevention or treatment of cold-like symptoms, prevention or treatment of viral infections, plasmacytoid dendritic cell activation, or promotion of interferon production. The above-mentioned lactic acid bacteria can be implemented in accordance with the description relating to the composition or agent of the present invention.

[0073] The methods or uses of the present invention may be used in mammals, including humans, and are intended for both therapeutic and non-therapeutic use. In this specification, “non-therapeutic” means not including any act of surgery, treatment or diagnosis of a human being (i.e., medical practice on a human being), and more specifically, not including any method of surgery, treatment or diagnosis of a human being performed on a human being by a physician or a person under the direction of a physician. [Examples]

[0074] The present invention will be described more specifically based on the following examples, but the present invention is not limited to these examples.

[0075] 1:pDCs react with IFN-α cells (1) In Example 1, we investigated the induction of IFN-α production by activation of lactic acid bacteria's pDCs.

[0076] (1) Method a. Preparation of lactic acid bacteria suspension The lactic acid bacteria used were those shown in Table 1, and each type was cultured under the culture conditions (culture method) shown in Table 2. Subsequently, the lactic acid bacteria were harvested, washed three times with sterile water, heat-sterilized at 80°C for 30 minutes, and then freeze-dried to obtain heat-killed cells. The heat-killed cells were then diluted with PBS (Takara Bio Inc.) to a concentration of 1 mg / mL to prepare a lactic acid bacteria suspension.

[0077] [Table 1]

[0078] [Table 2]

[0079] I. Test Procedure The test was conducted according to the following procedure (i) to (iv). (i) Female BALB / c mouse bone marrow cells are placed in RPMI medium (Sigma Corporation) prepared to the following composition in 1 × 10⁶ 6 The cells were suspended to a concentration of cells / mL to prepare a cell suspension. <Composition of culture medium> • 10% FBS by volume • 100 U / mL Penicillin / Streptomycin 1 mM sodium pyruvate 2.5mM HEPES 1% MEM NEAA 50 μM β-mercaptoethanol • 100 ng / mL Flt-3L (ii) The prepared cell suspension was seeded in 1 mL portions and cultured in a CO2 incubator at 37°C and 5% CO2 for 1 week to induce pDCs. (iii) Bone marrow cells containing induced pDCs, 2 × 10 5The lactic acid bacteria suspensions were resuspended to a concentration of 1 / mL, seeded in 200 μL portions into 96-well plates, and 2 μL of each of the above-mentioned lactic acid bacteria suspensions was added. On the other hand, the control (negative control) did not include the above-mentioned lactic acid bacteria suspension, and instead, 0.1 μM of CpG DNA (InvivoGen Ltd.) was added as the positive control. (iv) After 24 hours, the culture supernatant was collected and the IFN-α concentration was measured using an IFN-α measurement kit (PBL Assay Science Ltd.).

[0080] (2) Results The results are shown in Figure 2. Of the 22 types of lactic acid bacteria, nine (Lactococcus plantarum JCM11056, Lentilactobacillus parakefiri JCM8573, Leuconostoc carnosum JCM9695, Tetragenococcus halophilus NRIC0098, Oenococcus oeni JCM6125, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Bifidobacterium animalis subspecies lactis JCM10602, and Bifidobacterium longum subspecies infantis JCM1222) were confirmed to have IFN-α concentrations exceeding 30 pg / mL. These results indicate that these nine types of lactic acid bacteria can induce IFN-α production by activating pDCs and thus possess immunostimulatory effects.

[0081] 2: pDCs are responsible for IFN-α expression (2) In Example 2, we further investigated the two types of lactic acid bacteria that showed high IFN-α concentrations in Example 1.

[0082] (1) Method a. Preparation of lactic acid bacteria suspension Lactic acid bacteria suspensions were prepared in the same manner as described in Example 1(1)a, except that two types of lactic acid bacteria, Oenococcus oeni JCM6125 and Bifidobacterium animalis subspecies lactis JCM10602, were used, and the lactic acid bacteria were adjusted to concentrations of 1 mg / mL, 0.5 mg / mL, and 0.1 mg / mL.

[0083] I. Test Procedure The test was conducted using the same procedure as described in Example 1(1)i.

[0084] (2) Results The results are shown in Figure 3. Both Oenococcus oeni JCM6125 and Bifidobacterium animalis subspecies lactis JCM10602 produced IFN-α exceeding 480 pg / mL at a concentration of 0.1 mg / mL, and IFN-α production exceeded 1200 pg / mL at concentrations of 0.5 mg / mL and 1 mg / mL. These results indicate that these two types of lactic acid bacteria have a particularly high ability to induce IFN-α production by activating pDCs, and possess excellent immunostimulatory effects.

[0085] 3:pDCs are responsible for IFN-α expression (3) In Example 3, we investigated the induction of IFN-α production by pDC activation of lactic acid bacteria contained in commercially available products.

[0086] (1) Method a. Preparation of lactic acid bacteria suspension The lactic acid bacteria used were those contained in the commercially available products shown in Table 3. A portion of the commercially available products was dispersed in PBS, and the lactic acid bacteria were recovered by performing a washing procedure twice (centrifugation, discarding the supernatant, and adding PBS to disperse). Then, each of the recovered lactic acid bacteria was dispersed in PBS and adjusted to the concentrations shown in Table 3 to prepare lactic acid bacteria suspensions.

[0087] [Table 3]

[0088] I. Test Procedure The test was conducted using the same procedure as described in Example 1(1)i.

[0089] (2) Results The results are shown in Figure 4. Two types of lactic acid bacteria, Lactobacillus gasseri SBT2055 strain and Lactobacillus plantarum L-137 strain, were confirmed to induce IFN-α production through pDC activation, but IFN-α production was not observed in any other types of lactic acid bacteria.

[0090] 4: pDCs are responsible for IFN-α expression (4) In Example 4, we investigated the induction of IFN-α production by pDC activation of components contained in commercially available products.

[0091] (1) Method a. Preparation of suspension Quercetin (Sigma-America, part number: Q4951) and catechin (Fujifilm Wako Pure Chemical Industries, part number: 038-23461) were extracted, dispersed in PBS, and suspensions at concentrations of 0.001 mg / mL, 0.01 mg / mL, 0.1 mg / mL, and 1 mg / mL were prepared.

[0092] I. Test Procedure The test was conducted using the same procedure as described in Example 1(1)i.

[0093] (2) Results The results are shown in Figure 5. No IFN-α production was observed by quercetin or catechin.

[0094] 5: pDCs are responsible for IFN-α expression (5) In Example 5, we investigated the induction of IFN-α production by pDC activation of acetic acid bacteria contained in commercially available products.

[0095] (1) Method a. Preparation of Acetic Acid Bacteria Suspension Acetic acid bacteria were used from commercially available products shown in Table 4. A portion of the commercially available products was dispersed in PBS, and the acetic acid bacteria were recovered by performing a washing procedure twice (centrifugation, discarding the supernatant, and adding PBS to disperse). Then, each recovered acetic acid bacteria was dispersed in PBS and adjusted to the concentrations shown in Table 3 to prepare acetic acid bacteria suspensions.

[0096] [Table 4]

[0097] I. Test Procedure The test was conducted using the same procedure as described in Example 1(1)i.

[0098] (2) Results The results are shown in Figure 6. No IFN-α production was observed in the gluconacetobacter hanzenii GK-1 strain.

Claims

1. An immunostimulatory composition comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria is one or more selected from the group consisting of Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, Lentilactobacillus parakefilii JCM8573, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Tetragenococcus halophilus NRIC0098, Lactococcus plantarum JCM11056, and Leuconostoc carnosum JCM9695, and the composition is an oral ingestion composition.

2. A composition for preventing or treating cold-like symptoms, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria is one or more selected from the group consisting of Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, Lentilactobacillus parakefilii JCM8573, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Tetragenococcus halophilus NRIC0098, Lactococcus plantarum JCM11056, and Leuconostoc carnosum JCM9695, and the composition is an orally administered composition.

3. A composition for the prevention or treatment of viral infection, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria is one or more selected from the group consisting of Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, Lentilactobacillus parakefilii JCM8573, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Tetragenococcus halophilus NRIC0098, Lactococcus plantarum JCM11056, and Leuconostoc carnosum JCM9695, and the composition is an orally administered composition.

4. A composition for activating plasmacytoid dendritic cells, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria are one or more selected from the group consisting of Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, Lentilactobacillus parakefilii JCM8573, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Tetragenococcus halophilus NRIC0098, Lactococcus plantarum JCM11056, and Leuconostoc carnosum JCM9695, and the composition is an orally administered composition.

5. A composition for promoting interferon production, comprising lactic acid bacteria as an active ingredient, wherein the lactic acid bacteria is one or more selected from the group consisting of Oenococcus oeni JCM6125, Bifidobacterium animalis subspecies lactis JCM10602, Bifidobacterium longum subspecies infantis JCM1222, Lentilactobacillus parakefilii JCM8573, Weissella paramesenteroides JCM9890, Weissella viridesens JCM1174, Tetragenococcus halophilus NRIC0098, Lactococcus plantarum JCM11056, and Leuconostoc carnosum JCM9695, and the composition is an orally administered composition.

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