# Immunomodulatory functional foods and their molecular mechanisms

**Authors:** Jae Hwan Kim, Da Hyun Kim, Seongin Jo, Min Je Cho, Ye Ryeong Cho, Yong Joon Lee, Sanguine Byun

PMC · DOI: 10.1038/s12276-022-00724-0 · 2022-01-25

## TL;DR

This paper reviews how certain functional foods can boost immune function and protect against diseases by modulating immune cell activity.

## Contribution

The paper provides a comprehensive review of functional foods and their molecular mechanisms in modulating the immune system.

## Key findings

- Functional foods like ginseng and probiotics can enhance immune cell activity.
- Biochemicals in these foods influence both innate and adaptive immunity.
- Poly-gamma-glutamate is one component shown to modulate immune responses.

## Abstract

The immune system comprises a complex group of processes that provide defense against diverse pathogens. These defenses can be divided into innate and adaptive immunity, in which specific immune components converge to limit infections. In addition to genetic factors, aging, lifestyle, and environmental factors can influence immune function, potentially affecting the susceptibility of the host to disease-causing agents. Chemical compounds in certain foods have been shown to regulate signal transduction and cell phenotypes, ultimately impacting pathophysiology. Research has shown that the consumption of specific functional foods can stimulate the activity of immune cells, providing protection against cancer, viruses, and bacteria. Here, we review a number of functional foods reported to strengthen immunity, including ginseng, mushrooms, chlorella, and probiotics (Lactobacillus plantarum). We also discuss the molecular mechanisms involved in regulating the activity of various types of immune cells. Identifying immune-enhancing functional foods and understanding their mechanisms of action will support new approaches to maintain proper health and combat immunological diseases.

Evidence is building to support the idea that specific ‘functional foods’ can stimulate the activity of cells and signaling systems of the immune system to provide protection against cancer, viruses and bacteria. Sanguine Byun and colleagues at Yonsei University in Seoul, South Korea, review research into a range of functional foods, foods thought to have health benefits beyond their nutritional value. These include ginseng, mushrooms, the green algae called Chlorella and the probiotic bacteria Lactobacillus plantarum. They also consider individual components of foods such as poly-gamma-glutamate, a natural polymer made by bacteria. A wide body of research is revealing diverse molecular mechanisms through which biochemicals in functional foods can modulate different aspects of the immune system. These include effects on both non-specific innate immunity and adaptive immunity, which targets specific invading pathogens and diseased cells.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, Il12b (interleukin 12b) [NCBI Gene 16160] {aka Il-12b, Il-12p40, Il12p40, p40}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, Hand2 (heart and neural crest derivatives expressed 2) [NCBI Gene 15111] {aka Ehand2, Hed, Th2, Thing2, bHLHa26, dHAND}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Igh-V7183 (immunoglobulin heavy chain (V7183 family)) [NCBI Gene 16059] {aka B9-scFv, IgG, IgH, IgVH1(VSG), VH7183, VI24H}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Ncr1 (natural cytotoxicity triggering receptor 1) [NCBI Gene 17086] {aka Cd335, Ly94, NKp46}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Nf1 (neurofibromin 1) [NCBI Gene 18015] {aka Dsk9, E030030H24Rik, Mhdadsk9, Nf-1}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Nelfcd (negative elongation factor complex member C/D, Th1l) [NCBI Gene 57314] {aka 2410003I03Rik, NELF-D, Th1, Th1l}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Dcn (decorin) [NCBI Gene 13179] {aka DC, DSPG2, PG40, PGII, PGS2, SLRR1B}, Cd69 (CD69 antigen) [NCBI Gene 12515] {aka 5830438K24Rik, AIM, VEA}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, Clec7a (C-type lectin domain family 7, member a) [NCBI Gene 56644] {aka BGR, Clecsf12, beta-GR}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Serpinb1-ps1 (serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene) [NCBI Gene 282665] {aka EID, ovalbumin}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, CRIPTO3 (cripto, EGF-CFC family member 3) [NCBI Gene 6998] {aka CR-3, CRIPTO-3, TDGF1, TDGF1P3, TDGF2, TDGF3}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, Igkv14-126 (immunoglobulin kappa variable 14-126) [NCBI Gene 628127] {aka EG628127, Gm6844, IgK, IgM, br9, mga5th128}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, LOC105243590 (Ig heavy chain Mem5-like) [NCBI Gene 105243590] {aka IgH, Igg1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}
- **Diseases:** weight loss (MESH:D015431), ARI (MESH:D012120), breast cancer (MESH:D001943), bacterial infections (MESH:D001424), rabies (MESH:D011818), inflammatory cytokines (MESH:D000080424), immunological diseases (MESH:D007154), CIN 1 (MESH:D002578), parasite infection (MESH:D010272), lung cancer (MESH:D008175), viral (MESH:D014777), parasitemia (MESH:D018512), herpesvirus (MESH:D006566), microbial infections (MESH:D015163), cancer (MESH:D009369), infection of influenza viruses (MESH:D007251), CM (MESH:D016779), lung metastasis (MESH:D009362), infection (MESH:D007239), infectious diseases (MESH:D003141), colon cancer (MESH:D015179), leukemia (MESH:D007938), reproductive failure (MESH:D051437), melanoma (MESH:D008545), MDS (MESH:D009190), E. coli infection (MESH:D004927)
- **Chemicals:** beta-glucan (MESH:D047071), Ginsenoside (MESH:D036145), water (MESH:D014867), Ginsenoside Rc (MESH:C044462), C. pyrenoidosa (-), polysaccharide (MESH:D011134), Se (MESH:D012643), NO (MESH:D009569), EPS (MESH:C100219), Ginsenoside Rd (MESH:C049863), amide (MESH:D000577), ginsenoside Re (MESH:C049864), cyclophosphamide (MESH:D003520), Ginsan (MESH:C111520), gamma-PGA (MESH:C511775), oligopeptides (MESH:D009842), Ginsenoside Rb1 (MESH:C442759), Ginsenoside Rg1 (MESH:C035054), Re (MESH:D012211), lipid (MESH:D008055)
- **Species:** Panax ginseng (Asiatic ginseng, species) [taxon 4054], H1N1 subtype (serotype) [taxon 114727], Grifola frondosa (hen-of-the-woods, species) [taxon 5627], Sus scrofa (pig, species) [taxon 9823], Enterovirus (genus) [taxon 12059], Chlorella vulgaris (species) [taxon 3077], Rattus norvegicus (brown rat, species) [taxon 10116], Influenza A virus (no rank) [taxon 11320], Lactiplantibacillus plantarum (species) [taxon 1590], Porcine parvovirus (no rank) [taxon 10796], PX clade (clade) [taxon 569578], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Salmonella (genus) [taxon 590], Auxenochlorella pyrenoidosa (species) [taxon 3078], Homo sapiens (human, species) [taxon 9606], Lyssavirus rabies (species) [taxon 11292], Escherichia coli (E. coli, species) [taxon 562], Glycine max (soybean, species) [taxon 3847], Toxoplasma gondii (species) [taxon 5811], Human papillomavirus (species) [taxon 10566], Listeria monocytogenes (species) [taxon 1639], Ganoderma lucidum (species) [taxon 5315], Bacillus subtilis subsp. chungkookjang (subspecies) [taxon 118965], Candida albicans (species) [taxon 5476], Gammacoronavirus (genus) [taxon 694013], Mus musculus (house mouse, species) [taxon 10090], Suid alphaherpesvirus 1 (no rank) [taxon 10345], chlorella [taxon 114055], Agaricus blazei (species) [taxon 79798], Agaricus bisporus (common mushroom, species) [taxon 5341], Plasmodium berghei (species) [taxon 5821], Pseudomonas aeruginosa (species) [taxon 287], Gallus gallus (bantam, species) [taxon 9031]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), BALB/ — Mus musculus (Mouse), Transformed cell line (CVCL_4350), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), MOLT-4 — Homo sapiens (Human), Adult T acute lymphoblastic leukemia, Cancer cell line (CVCL_0013), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184)

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Source: https://tomesphere.com/paper/PMC8787967