MİKROBİYOM VE BAĞIŞIKLIK SİSTEMİ ARASINDAKİ ETKİLEŞİM: HOMEOSTAZ VE TOLERANS MEKANİZMALARI

Year 2025, Volume: 16 Issue: 2, 53 - 63, 31.08.2025

Abdoul Bassirou Ouedraogo , Efsun Melike Çeçen , Murat Yıldırım

https://doi.org/10.38137/vftd.1618052

Abstract

Mikrobiyom, özellikle mukozal yüzeylerin kolonize olduğu erken yaşam döneminde, sağlığın korunmasında ve fizyolojik süreçlerin etkilenmesinde önemli bir rol oynar. Kolonizasyon, bireyin yaşamı boyunca devam eden bağışıklık tepkilerini şekillendirir. Son zamanlarda yapılan çalışmalar, mikrobiyomun sindirim sağlığının ötesinde, özellikle bağışıklık tepkilerinin düzenlenmesindeki önemini vurgulamıştır. Bağırsak ve diğer mukozal bölgelerdeki çeşitli mikrobiyal topluluklar, bağışıklık hücrelerinin gelişimine ve bağışıklık toleransının modülasyonuna katkıda bulunarak konağın zararlı patojenler ile faydalı mikroorganizmalar arasında ayrım yapmasını sağlar. Bu dengedeki bozulmalar, otoimmün hastalıklar ve alerjilerle sonuçlanan bağışıklık fonksiyon bozukluğuna yol açabilir. Mikrobiyom ve bağışıklık sistemi arasındaki etkileşimlerin altında yatan mekanizmaların anlaşılması, bağışıklık sağlığını iyileştirmeyi ve hastalıkları önlemeyi amaçlayan terapötik stratejiler geliştirmek için gereklidir. Bu derleme, mikrobiyomun bağışıklık sisteminin gelişimindeki rolünü, mikrobiyota ve bağışıklık sistemi arasındaki etkileşimi ve konak mikrobiyota tolerans mekanizmalarını ortaya koymayı amaçlamaktadır.

Keywords

Bağışıklık sistemi , Homeostaz , İmmün tolerans , Mikrobiyom

INTERACTION BETWEEN MICROBIOME AND IMMUNE SYSTEM: MECHANISMS OF HOMEOSTASIS AND TOLERANCE

Abstract

The microbiome plays a significant role in maintaining health and influencing physiological processes, especially during early life when mucosal surfaces are colonized. Colonization shapes immune responses that continue throughout an individual's life. Recent studies have emphasized the importance of the microbiome beyond digestive health, particularly in the regulation of immune responses. Diverse microbial communities in the gut and other mucosal sites contribute to the development of immune cells and the modulation of immune tolerance, enabling the host to differentiate between harmful pathogens and beneficial microorganisms. Disruptions in this balance can lead to immune dysfunction, resulting in autoimmune diseases and allergies. Understanding the underlying mechanisms of interaction between the microbiome and the immune system is essential for developing therapeutic strategies aimed at improving immune health and preventing diseases. This review aims to elucidate the role of the microbiome in the development of the immune system, the interaction between the microbiota and the immune system, and host-microbiota tolerance mechanisms.

Keywords

Microbiome , Immune system , Homeostasis , Immune tolerance

References

• Aagaard, K., Ma, J., Antony, K. M., Ganu, R., Petrosino, J. & Versalovic, J. (2014). The placenta harbors a unique microbiome. Science Translational Medicine, 6(237), 237ra65.
• Ahuja, M., Schwartz, D. M., Tandon, M., Son, A., Zeng, M., Swaim, W., Eckhaus, M., Hoffman, V., Cui, Y., Xiao, B., Worley, P. F. & Muallem, S. (2017). Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metabolism, 25(3), 635–646.
• Amarante-Mendes, G. P., Adjemian, S., Branco, L. M., Zanetti, L. C., Weinlich, R. & Bortoluci, K. R. (2018). Pattern recognition receptors and the host cell death molecular machinery. Frontiers in Immunology, 9, 2379. An, D., Oh, S. F., Olszak, T., Neves, J. F., Avci, F. Y., Erturk-Hasdemir, D., Lu, X., Zeissig, S., Blumberg, R. S. & Kasper, D. L. (2014). Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell, 156(1–2), 123–133.
• Arike, L., Seiman, A., van der Post, S., Rodriguez Piñeiro, A. M., Ermund, A., Schütte, A., Bäckhed, F., Johansson, M. E. V. & Hansson, G. C. (2020). Protein turnover in epithelial cells and mucus along the gastrointestinal tract is coordinated by the spatial location and microbiota. Cell Reports, 30(4), 1077–1087.e3.
• Arpaia, N. & Rudensky, A. Y. (2014). Microbial metabolites control gut inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America, 111(6), 2058–2059.
• Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J. & Rudensky, A. Y. (2013). Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 504(7480), 451–455.
• Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., Ishikawa, E., Shima, T., Hara, T., Kado, S., Jinnohara, T., Ohno, H., Kondo, T., Toyooka, K., Watanabe, E., Yokoyama, S. & Honda, K. (2015). Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell, 163(2), 367–380.
• Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., Li, Y., Xia, Y., Xie, H., Zhong, H., Khan, M. T., Zhang, J., Li, J., Xiao, L., Al-Aama, J., Zhang, D., Lee, Y. S., Kotowska, D., Colding, C., Tremaroli, V. & Wang, J. (2015). Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host & Microbe, 17(5), 690–703.
• Bauer, H., Horowitz, R. E., Levenson, S. M. & Popper, H. (1963). The response of the lymphatic tissue to the microbial flora: Studies on germfree mice. American Journal of Pathology, 42(4), 471–483. Bedoui, S., Heath, W. R. & Mueller, S. N. (2016). CD4(+) T-cell help amplifies innate signals for primary CD8(+) T-cell immunity. Immunological Reviews, 272(1), 52–64.
• Berg, G., Rybakova, D., Fischer, D., Cernava, T., Vergès, M. C., Charles, T., Chen, X., Cocolin, L., Eversole, K., Corral, G. H., Kazou, M., Kinkel, L., Lange, L., Lima, N., Loy, A., Macklin, J. A., Maguin, E., Mauchline, T., McClure, R., Mitter, B. & Schloter, M. (2020). Microbiome definition revisited: Old concepts and new challenges. Microbiome, 8(1), 103. Bevins, C. L. & Salzman, N. H. (2011). Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nature Reviews Microbiology, 9(5), 356–368.
• Bianchi, M. E. (2007). DAMPs, PAMPs and alarmins: All we need to know about danger. Journal of Leukocyte Biology, 81(1), 1–5.
• Bouskra, D., Brézillon, C., Bérard, M., Werts, C., Varona, R., Boneca, I. G. & Eberl, G. (2008). Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature, 456(7221), 507–510.
• Butler, J. E., Santiago-Mateo, K., Wertz, N., Sun, X., Sinkora, M. & Francis, D. L. (2016). Antibody repertoire development in fetal and neonatal piglets. XXIV. Hypothesis: The ileal Peyer patches (IPP) are the major source of primary, undiversified IgA antibodies in newborn piglets. Developmental and Comparative Immunology, 65, 340–351.
• Cash, H. L., Whitham, C. V., Behrendt, C. L. & Hooper, L. V. (2006). Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science, 313(5790), 1126–1130.
• Chen, L., Zheng, L., Chen, P. & Liang, G. (2020). Myeloid differentiation primary response protein 88 (MyD88): The central hub of TLR/IL-1R signaling. Journal of Medicinal Chemistry, 63(22), 13316–13329.
• Cheng, J., Lei, H., Xie, C., Chen, J., Yi, X., Zhao, F., Yuan, Y., Chen, P., He, J., Luo, C., Shu, D., Qu, H. & Ji, J. (2023). B lymphocyte development in the bursa of Fabricius of young broilers is influenced by the gut microbiota. Microbiology Spectrum, 11(2), e0479922.
• Chua, H. H., Chou, H. C., Tung, Y. L., Chiang, B. L., Liao, C. C., Liu, H. H. & Ni, Y. H. (2018). Intestinal dysbiosis featuring abundance of Ruminococcus gnavus associates with allergic diseases in infants. Gastroenterology, 154(1), 154–167.
• Chudnovskiy, A., Mortha, A., Kana, V., Kennard, A., Ramirez, J. D., Rahman, A., Remark, R., Mogno, I., Ng, R., Gnjatic, S., Amir, E. A. D., Solovyov, A., Greenbaum, B., Clemente, J., Faith, J., Belkaid, Y., Grigg, M. E. & Merad, M. (2016). Host-protozoan interactions protect from mucosal infections through activation of the inflammasome. Cell, 167(2), 444–456.e14.
• Chun, E., Lavoie, S., Fonseca-Pereira, D., Bae, S., Michaud, M., Hoveyda, H. R., Fraser, G. L., Gallini Comeau, C. A., Glickman, J. N., Fuller, M. H., Layden, B. T. & Garrett, W. S. (2019). Metabolite-sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity. Immunity, 51(5), 871–884.e6.
• Constantinides, M. G., McDonald, B. D., Verhoef, P. A. & Bendelac, A. (2014). A committed precursor to innate lymphoid cells. Nature, 508(7496), 397–401.
• Crotty, S. (2014). T follicular helper cell differentiation, function, and roles in disease. Immunity, 41(4), 529–542.
• Danne, C., Ryzhakov, G., Martínez-López, M., Ilott, N. E., Franchini, F., Cuskin, F., Lowe, E. C., Bullers, S. J., Arthur, J. S. C. & Powrie, F. (2017). A large polysaccharide produced by Helicobacter hepaticus induces an anti-inflammatory gene signature in macrophages. Cell Host & Microbe, 22(6), 733–745.e5.
• Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N. & Knight, R. (2010). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences of the United States of America, 107(26), 11971–11975.
• Dutzan, N., Abusleme, L., Bridgeman, H., Greenwell-Wild, T., Zangerle-Murray, T., Fife, M. E., Bouladoux, N., Linley, H., Brenchley, L., Wemyss, K., Calderon, G., Hong, B. Y., Break, T. J., Bowdish, D. M. E., Lionakis, M. S., Jones, S. A., Trinchieri, G., Diaz, P. I., Belkaid, Y., Konkel, J. E. & Moutsopoulos, N. M. (2017). On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity, 46(1), 133–147.
• Earley, Z. M., Lisicka, W., Sifakis, J. J., Aguirre-Gamboa, R., Kowalczyk, A., Barlow, J. T., Shaw, D. G., Discepolo, V., Tan, I. L., Gona, S., Ernest, J. D., Matzinger, P., Barreiro, L. B., Morgun, A., Bendelac, A., Ismagilov, R. F., Shulzhenko, N., Riesenfeld, S. J. & Jabri, B. (2023). GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology. Immunity, 56(1), 43–57.e10.
• Ehmann, D., Wendler, J., Koeninger, L., Larsen, I. S., Klag, T., Berger, J., Marette, A., Schaller, M., Stange, E. F., Malek, N. P., Jensen, B. a. H., & Wehkamp, J. (2019). Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments. Proceedings of the National Academy of Sciences of the United States of America, 116(9), 3746-3751.
• Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I. & Flavell, R. A. (2011). NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell, 145(5), 745–757.
• Franchi, L., Amer, A., Body-Malapel, M., Kanneganti, T. D., Ozören, N., Jagirdar, R., Inohara, N., Vandenabeele, P., Bertin, J., Coyle, A., Grant, E. P. & Núñez, G. (2006). Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nature Immunology, 7(6), 576–582.
• Fulde, M., Sommer, F., Chassaing, B., van Vorst, K., Dupont, A., Hensel, M., Basic, M., Klopfleisch, R., Rosenstiel, P., Bleich, A., Bäckhed, F., Gewirtz, A. T. & Hornef, M. W. (2018). Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition. Nature, 560(7719), 489–493.
• Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., Eberl, G., Snel, J., Kelly, D. & Cerf-Bensussan, N. (2009). The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity, 31(4), 677–689.
• Gálvez, E. J. C., Iljazovic, A., Gronow, A., Flavell, R. & Strowig, T. (2017). Shaping of intestinal microbiota in Nlrp6- and Rag2-deficient mice depends on community structure. Cell Reports, 21(13), 3914–3926.
• Gomez de Agüero, M., Ganal-Vonarburg, S. C., Fuhrer, T., Rupp, S., Uchimura, Y., Li, H., Steinert, A., Heikenwalder, M., Hapfelmeier, S., Sauer, U., McCoy, K. D. & Macpherson, A. J. (2016). The maternal microbiota drives early postnatal innate immune development. Science, 351(6279), 1296–1302.
• Guo, X., Liang, Y., Zhang, Y., Lasorella, A., Kee, B. L. & Fu, Y. X. (2015). Innate lymphoid cells control early colonization resistance against intestinal pathogens through ID2-dependent regulation of the microbiota. Immunity, 42(4), 731–743.
• Gury-BenAri, M., Thaiss, C. A., Serafini, N., Winter, D. R., Giladi, A., Lara-Astiaso, D., Levy, M., Salame, T. M., Weiner, A., David, E., Shapiro, H., Dori-Bachash, M., Pevsner-Fischer, M., Lorenzo-Vivas, E., Keren-Shaul, H., Paul, F., Harmelin, A., Eberl, G., Itzkovitz, S., Tanay, A. & Amit, I. (2016). The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome. Cell, 166(5), 1231–1246.e13.
• Güçlü Durgun, S. & Deveci Özkan, A. (2021). Bağırsak mikrobiyotası ve toll benzeri reseptörler arasındaki ilişki: Bağışıklık ve metabolizma. Journal of Biotechnology and Strategic Health Research, 5(1), 12–21.
• Haase, S., Haghikia, A., Wilck, N., Müller, D. N. & Linker, R. A. (2018). Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology, 154(2), 230–238.
• Hapfelmeier, S., Lawson, M. A., Slack, E., Kirundi, J. K., Stoel, M., Heikenwalder, M., Cahenzli, J., Velykoredko, Y., Balmer, M. L., Endt, K., Geuking, M. B., Curtiss, R., McCoy, K. D. & Macpherson, A. J. (2010). Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science, 328(5986), 1705–1709.
• Hegazy, A. N., West, N. R., Stubbington, M. J. T., Wendt, E., Suijker, K. I. M., Datsi, A., This, S., Danne, C., Campion, S., Duncan, S. H., Owens, B. M. J., Uhlig, H. H., McMichael, A., Oxford IBD Cohort Investigators, Bergthaler, A., Teichmann, S. A., Keshav, S. & Powrie, F. (2017). Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology, 153(5), 1320–1337.e16.
• Heidari, M., Maleki Vareki, S., Yaghobi, R. & Karimi, M. H. (2024). Microbiota activation and regulation of adaptive immunity. Frontiers in Immunology, 15, 1498765.
• Hornung, V., Hartmann, R., Ablasser, A. & Hopfner, K. P. (2014). OAS proteins and cGAS: Unifying concepts in sensing and responding to cytosolic nucleic acids. Nature Reviews Immunology, 14(8), 521–528.
• Ignacio, A., Czyz, S. & McCoy, K. D. (2024). Early life microbiome influences on development of the mucosal innate immune system. Seminars in Immunology, 73, 101885.
• Ismail, A. S., Severson, K. M., Vaishnava, S., Behrendt, C. L., Yu, X., Benjamin, J. L., Ruhn, K. A., Hou, B., DeFranco, A. L., Yarovinsky, F. & Hooper, L. V. (2011). Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. Proceedings of the National Academy of Sciences of the United States of America, 108(21), 8743–8748.
• Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K. & Littman, D. R. (2009). Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 139(3), 485–498.
• İspir, F. & Yücelik, Ş. S. (2019). İnflamazomların karaciğer toksisitesindeki rolü. HUJPHARM, 39(2), 90–97.
• Jacobse, J., Li, J., Rings, E. H. H. M., Samsom, J. N. & Goettel, J. A. (2021). Intestinal regulatory T cells as specialized tissue-restricted immune cells in intestinal immune homeostasis and disease. Frontiers in Immunology, 12, 716499.
• Jie, Z., Yang, J. Y., Gu, M., Wang, H., Xie, X., Li, Y., Liu, T., Zhu, L., Shi, J., Zhang, L., Zhou, X., Joo, D., Brightbill, H. D., Cong, Y., Lin, D., Cheng, X. & Sun, S. C. (2018). NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. Nature Immunology, 19(11), 1224–1235.
• Jing, X., Zulfiqar, F., Park, S. Y., Núñez, G., Dziarski, R. & Gupta, D. (2014). Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from dextran sodium sulfate-induced colitis. Journal of Immunology, 193(6), 3055–3069.
• Jordan, C. K. I. & Clarke, T. B. (2024). How does the microbiota control systemic innate immunity? Trends in Immunology, 45(2), 94–102.
• Kawamoto, S., Maruya, M., Kato, L. M., Suda, W., Atarashi, K., Doi, Y., Tsutsui, Y., Qin, H., Honda, K., Okada, T., Hattori, M. & Fagarasan, S. (2014). Foxp3(+) T cells regulate immunoglobulin A selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity, 41(1), 152–165.
• Klatt, N. R., Funderburg, N. T. & Brenchley, J. M. (2013). Microbial translocation, immune activation, and HIV disease. Trends in Microbiology, 21(1), 6–13.
• Kubinak, J. L., Petersen, C., Stephens, W. Z., Soto, R., Bake, E., O’Connell, R. M. & Round, J. L. (2015). MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host & Microbe, 17(2), 153–163.
• Lauder, A. P., Roche, A. M., Sherrill-Mix, S., Bailey, A., Laughlin, A. L., Bittinger, K., Leite, R., Elovitz, M. A., Parry, S. & Bushman, F. D. (2016). Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome, 4(1), 29.
• Levy, M., Thaiss, C. A., Zeevi, D., Dohnalová, L., Zilberman-Schapira, G., Mahdi, J. A., David, E., Savidor, A., Korem, T., Herzig, Y., Pevsner-Fischer, M., Shapiro, H., Christ, A., Harmelin, A., Halpern, Z., Latz, E., Flavell, R. A., Amit, I., Segal, E. & Elinav, E. (2015). Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell, 163(6), 1428–1443.
• Liu, Y., Zhang, J., Yang, G., Tang, C., Li, X., Lu, L., Long, K., Sun, J., Ding, Y., Li, X., Li, M., Ge, L. & Ma, J. (2024). Effects of the commensal microbiota on spleen and mesenteric lymph node immune function: Investigation in a germ-free piglet model. Frontiers in Microbiology, 15, 1398631.
• Macpherson, A. J. & Uhr, T. (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science, 303(5664), 1662–1665.
• Macpherson, A. J., Slack, E., Geuking, M. B. & McCoy, K. D. (2009). The mucosal firewalls against commensal intestinal microbes. Seminars in Immunopathology, 31(2), 145–149.
• Martínez-López, M., Iborra, S., Conde-Garrosa, R., Mastrangelo, A., Danne, C., Mann, E. R., Reid, D. M., Gaboriau-Routhiau, V., Chaparro, M., Lorenzo, M. P., Minnerup, L., Saz-Leal, P., Slack, E., Kemp, B., Gisbert, J. P., Dzionek, A., Robinson, M. J., Rupérez, F. J., Cerf-Bensussan, N. & Sancho, D. (2019). Microbiota sensing by Mincle-Syk axis in dendritic cells regulates interleukin-17 and -22 production and promotes intestinal barrier integrity. Immunity, 50(2), 446–461.e9.
• Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell, 122(1), 107–118.
• Miossec, P., & Kolls, J. K. (2012). Targeting IL-17 and TH17 cells in chronic inflammation. Nature reviews. Drug discovery, 11(10), 763–776.
• Mosser, D. M., & Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nature reviews. Immunology, 8(12), 958–969.
• Mowat, A. M. (2018). To respond or not to respond: A personal perspective of intestinal tolerance. Nature Reviews Immunology, 18(6), 405–415.
• Nagashima, K., Sawa, S., Nitta, T., Tsutsumi, M., Okamura, T., Penninger, J. M., Nakashima, T. & Takayanagi, H. (2017). Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nature Immunology, 18(6), 675–682.
• Naik, S., Bouladoux, N., Wilhelm, C., Molloy, M. J., Salcedo, R., Kastenmuller, W., Deming, C., Quinones, M., Koo, L., Conlan, S., Spencer, S., Hall, J. A., Dzutsev, A., Kong, H., Campbell, D. J., Trinchieri, G., Segre, J. A. & Belkaid, Y. (2012). Compartmentalized control of skin immunity by resident commensals. Science, 337(6098), 1115–1119.
• Nigro, G., Rossi, R., Commere, P. H., Jay, P. & Sansonetti, P. J. (2014). The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host & Microbe, 15(6), 792–798.
• Omenetti, S., Bussi, C., Metidji, A., Iseppon, A., Lee, S., Tolaini, M., Li, Y., Kelly, G., Chakravarty, P., Shoaie, S., Gutierrez, M. G. & Stockinger, B. (2019). The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory Th17 cells. Immunity, 51(1), 77–89.e6.
• Palm, N. W., de Zoete, M. R., Cullen, T. W., Barry, N. A., Stefanowski, J., Hao, L., Degnan, P. H., Hu, J., Peter, I., Zhang, W., Ruggiero, E., Cho, J. H., Goodman, A. L. & Flavell, R. A. (2014). Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell, 158(5), 1000–1010.
• Pannaraj, P. S., Li, F., Cerini, C., Bender, J. M., Yang, S., Rollie, A., Adisetiyo, H., Zabih, S., Lincez, P. J., Bittinger, K., Bailey, A., Bushman, F. D., Sleasman, J. W. & Aldrovandi, G. M. (2017). Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatrics, 171(7), 647–654.
• Peterson, D. A., McNulty, N. P., Guruge, J. L. & Gordon, J. I. (2007). IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host & Microbe, 2(5), 328–339.
• Proietti, M., Cornacchione, V., Rezzonico Jost, T., Romagnani, A., Faliti, C. E., Perruzza, L., Rigoni, R., Radaelli, E., Caprioli, F., Preziuso, S., Brannetti, B., Thelen, M., McCoy, K. D., Slack, E., Traggiai, E. & Grassi, F. (2014). ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer’s patches to promote host-microbiota mutualism. Immunity, 41(5), 789–801.
• Qiu, J., Guo, X., Chen, Z. M., He, L., Sonnenberg, G. F., Artis, D., Fu, Y. X. & Zhou, L. (2013). Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity, 39(2), 386–399.
• Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. (2004). Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell, 118(2), 229–241. Ramakrishna, C., Kujawski, M., Chu, H., Li, L., Mazmanian, S. K. & Cantin, E. M. (2019). Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis. Nature Communications, 10(1), 2153.
• Ramanan, D., Tang, M. S., Bowcutt, R., Loke, P. & Cadwell, K. (2014). Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus. Immunity, 41(2), 311–324.
• Rankin, L. C., Girard-Madoux, M. J., Seillet, C., Mielke, L. A., Kerdiles, Y., Fenis, A., Wieduwild, E., Putoczki, T., Mondot, S., Lantz, O., Demon, D., Papenfuss, A. T., Smyth, G. K., Lamkanfi, M., Carotta, S., Renauld, J. C., Shi, W., Carpentier, S., Soos, T., Arendt, C. & Vivier, E. (2016). Complementarity and redundancy of IL-22-producing innate lymphoid cells. Nature Immunology, 17(2), 179–186.
• Ratsimandresy, R. A., Indramohan, M., Dorfleutner, A. & Stehlik, C. (2017). The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway. Cellular & Molecular Immunology, 14(1), 127–142.
• Rescigno, M., Rotta, G., Valzasina, B. & Ricciardi-Castagnoli, P. (2001). Dendritic cells shuttle microbes across gut epithelial monolayers. Immunobiology, 204(5), 572–581.
• Saha, S., Jing, X., Park, S. Y., Wang, S., Li, X., Gupta, D. & Dziarski, R. (2010). Peptidoglycan recognition proteins protect mice from experimental colitis by promoting normal gut flora and preventing induction of interferon-gamma. Cell Host & Microbe, 8(2), 147–162.
• Schnell, A., Littman, D. R. & Kuchroo, V. K. (2023). TH17 cell heterogeneity and its role in tissue inflammation. Nature Immunology, 24(1), 19–29.
• Seo, S. U., Kamada, N., Muñoz-Planillo, R., Kim, Y. G., Kim, D., Koizumi, Y., Hasegawa, M., Himpsl, S. D., Browne, H. P., Lawley, T. D., Mobley, H. L., Inohara, N. & Núñez, G. (2015). Distinct commensals induce interleukin-1β via NLRP3 inflammasome in inflammatory monocytes to promote intestinal inflammation in response to injury. Immunity, 42(4), 744–755.
• Shan, M., Gentile, M., Yeiser, J. R., Walland, A. C., Bornstein, V. U., Chen, K., He, B., Cassis, L., Bigas, A., Cols, M., Comerma, L., Huang, B., Blander, J. M., Xiong, H., Mayer, L., Berin, C., Augenlicht, L. H. & Cerutti, A. (2013). Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science, 342(6157), 447–453.
• Shao, T., Hsu, R., Rafizadeh, D. L., Wang, L., Bowlus, C. L., Kumar, N., Mishra, J., Timilsina, S., Ridgway, W. M., Gershwin, M. E., Ansari, A. A., Shuai, Z. & Leung, P. S. C. (2023). The gut ecosystem and immune tolerance. Journal of Autoimmunity, 141, 103114.
• Shim, J. A., Ryu, J. H., Jo, Y. & Hong, C. (2023). The role of gut microbiota in T cell immunity and immune mediated disorders. International Journal of Biological Sciences, 19(4), 1178–1191.
• Shulzhenko, N., Morgun, A., Hsiao, W., Battle, M., Yao, M., Gavrilova, O., Orandle, M., Mayer, L., Macpherson, A. J., McCoy, K. D., Fraser-Liggett, C. & Matzinger, P. (2011). Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nature Medicine, 17(12), 1585–1593.
• Sims, M. C., Mayer, L., Collins, J. H., Bariana, T. K., Megy, K., Lavenu-Bombled, C., Seyres, D., Kollipara, L., Burden, F. S., Greene, D., Lee, D., Rodriguez-Romera, A., Alessi, M. C., Astle, W. J., Bahou, W. F., Bury, L., Chalmers, E., Da Silva, R., De Candia, E., Deevi, S. V. V. & Guerrero, J. A. (2020). Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome. Blood, 136(17), 1956–1967.
• Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N. & Garrett, W. S. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341(6145), 569–573.
• Song, X., Sun, X., Oh, S. F., Wu, M., Zhang, Y., Zheng, W., Geva-Zatorsky, N., Jupp, R., Mathis, D., Benoist, C. & Kasper, D. L. (2020). Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature, 577(7790), 410–415.
• Sutherland, D. B., Suzuki, K. & Fagarasan, S. (2016). Fostering of advanced mutualism with gut microbiota by immunoglobulin A. Immunological Reviews, 270(1), 20–31.
• Tan, T. G., Sefik, E., Geva-Zatorsky, N., Kua, L., Naskar, D., Teng, F., Pasman, L., Ortiz-Lopez, A., Jupp, R., Wu, H. J., Kasper, D. L., Benoist, C. & Mathis, D. (2016). Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proceedings of the National Academy of Sciences of the United States of America, 113(50), E8141–E8150.
• Teng, F., Klinger, C. N., Felix, K. M., Bradley, C. P., Wu, E., Tran, N. L., Umesaki, Y. & Wu, H. J. (2016). Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer’s patch T follicular helper cells. Immunity, 44(4), 875–888.
• Tizard, I. R. & Jones, S. W. (2018). The microbiota regulates immunity and immunologic diseases in dogs and cats. Veterinary Clinics of North America: Small Animal Practice, 48(2), 307–322.
• Umesaki, Y., Setoyama, H., Matsumoto, S. & Okada, Y. (1993). Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology, 79(1), 32–37.
• Vaishnava, S., Yamamoto, M., Severson, K. M., Ruhn, K. A., Yu, X., Koren, O., Ley, R., Wakeland, E. K. & Hooper, L. V. (2011). The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science, 334(6053), 255–258.
• Wang, R., Lan, C., Benlagha, K., Camara, N. O. S., Miller, H., Kubo, M., Heegaard, S., Lee, P., Yang, L., Forsman, H., Li, X., Zhai, Z. & Liu, C. (2024). The interaction of innate immune and adaptive immune system. MedComm, 5(10), e714.
• Wang, S., Charbonnier, L. M., Noval Rivas, M., Georgiev, P., Li, N., Gerber, G., Bry, L. & Chatila, T. A. (2015). MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity, 43(2), 289–303.
• Wei, M., Shinkura, R., Doi, Y., Maruya, M., Fagarasan, S. & Honjo, T. (2011). Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nature Immunology, 12(3), 264–270.
• Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., Gordon, J. I. & Chervonsky, A. V. (2008). Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature, 455(7216), 1109–1113.
• Wesemann, D. R., Portuguese, A. J., Meyers, R. M., Gallagher, M. P., Cluff-Jones, K., Magee, J. M., Panchakshari, R. A., Rodig, S. J., Kepler, T. B. & Alt, F. W. (2013). Microbial colonization influences early B-lineage development in the gut lamina propria. Nature, 501(7465), 112–115.
• Wingender, G., Hiss, M., Engel, I., Peukert, K., Ley, K., Haller, H., Kronenberg, M. & von Vietinghoff, S. (2012). Neutrophilic granulocytes modulate invariant NKT cell function in mice and humans. Journal of Immunology, 188(7), 3000–3008.
• Zenewicz, L. A. & Flavell, R. A. (2011). Recent advances in IL-22 biology. International Immunology, 23(3), 159–163.
• Zhang, C., Liu, H., Sun, L., Wang, Y., Chen, X., Du, J., Sjöling, Å., Yao, J. & Wu, S. (2023). An overview of host-derived molecules that interact with gut microbiota. iMeta, 2(2), e88.
• Zheng, D., Liwinski, T. & Elinav, E. (2020). Interaction between microbiota and immunity in health and disease. Cell Research, 30(6), 492–506.
• Zheng, W., Zhao, W., Wu, M., Song, X., Caro, F., Sun, X., Gazzaniga, F., Stefanetti, G., Oh, S., Mekalanos, J. J. & Kasper, D. L. (2020). Microbiota-targeted maternal antibodies protect neonates from enteric infection. Nature, 577(7791), 543–548.
• Zhu, H., Xu, W. Y., Hu, Z., Zhang, H., Shen, Y., Lu, S., Wei, C. & Wang, Z. G. (2017). RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer. Journal of Experimental & Clinical Cancer Research, 36(1), 2.