1932

Abstract

The immune system has coevolved with extensive microbial communities living on barrier sites that are collectively known as the microbiota. It is increasingly clear that microbial antigens and metabolites engage in a constant dialogue with the immune system, leading to microbiota-specific immune responses that occur in the absence of inflammation. This form of homeostatic immunity encompasses many arms of immunity, including B cell responses, innate-like T cells, and conventional T helper and T regulatory responses. In this review we summarize known examples of innate-like T cell and adaptive immunity to the microbiota, focusing on fundamental aspects of commensal immune recognition across different barrier sites. Furthermore, we explore how this cross talk is established during development, emphasizing critical temporal windows that establish long-term immune function. Finally, we highlight how dysregulation of immunity to the microbiota can lead to inflammation and disease, and we pinpoint outstanding questions and controversies regarding immune system–microbiota interactions.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-093019-112348
2021-04-26
2024-04-22
Loading full text...

Full text loading...

/deliver/fulltext/immunol/39/1/annurev-immunol-093019-112348.html?itemId=/content/journals/10.1146/annurev-immunol-093019-112348&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Sender R, Fuchs S, Milo R 2016. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:3337–40
    [Google Scholar]
  2. 2. 
    Dethlefsen L, McFall-Ngai M, Relman DA. 2007. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449:811–18
    [Google Scholar]
  3. 3. 
    Collins N, Belkaid Y. 2018. Do the microbiota influence vaccines and protective immunity to pathogens? Engaging our endogenous adjuvants. Cold Spring Harb. Perspect. Biol. 10:2a028860
    [Google Scholar]
  4. 4. 
    Kroemer G, Zitvogel L. 2018. Cancer immunotherapy in 2017: the breakthrough of the microbiota. Nat. Rev. Immunol. 18:287–88
    [Google Scholar]
  5. 5. 
    Belkaid Y, Harrison OJ. 2017. Homeostatic immunity and the microbiota. Immunity 46:4562–76
    [Google Scholar]
  6. 6. 
    Blander JM, Longman RS, Iliev ID, Sonnenberg GF, Artis D. 2017. Regulation of inflammation by microbiota interactions with the host. Nat. Immunol. 18:8851–60
    [Google Scholar]
  7. 7. 
    Tilg H, Zmora N, Adolph TE, Elinav E. 2020. The intestinal microbiota fuelling metabolic inflammation. Nat. Rev. Immunol. 20:140–54
    [Google Scholar]
  8. 8. 
    Byrd AL, Segre JA. 2016. Adapting Koch's postulates: Criteria for disease causation must take microbial interactions into account. Science 351:6270224–26
    [Google Scholar]
  9. 9. 
    Gollwitzer ES, Marsland BJ. 2015. Impact of early-life exposures on immune maturation and susceptibility to disease. Trends Immunol. 36:11684–96
    [Google Scholar]
  10. 10. 
    Reynolds LA, Finlay BB. 2017. Early life factors that affect allergy development. Nat. Rev. Immunol. 17:8518–28
    [Google Scholar]
  11. 11. 
    Kotas ME, Medzhitov R. 2015. Homeostasis, inflammation, and disease susceptibility. Cell 165:5816–27
    [Google Scholar]
  12. 12. 
    Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H et al. 2015. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17:5690–703
    [Google Scholar]
  13. 13. 
    Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. 2014. The placenta harbors a unique microbiome. Sci. Transl. Med. 6:237237ra65
    [Google Scholar]
  14. 14. 
    Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. 2016. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci. Rep. 6:23129
    [Google Scholar]
  15. 15. 
    Hornef M, Penders J. 2017. Does a prenatal bacterial microbiota exist?. Mucosal Immunol. 10:3598–601
    [Google Scholar]
  16. 16. 
    de Goffau MC, Lager S, Sovio U, Gaccioli F, Cook E et al. 2019. Human placenta has no microbiome but can contain potential pathogens. Nature 572:7769329–34
    [Google Scholar]
  17. 17. 
    Sibley CP, Brownbill P, Glazier JD, Greenwood SL. 2018. Knowledge needed about the exchange physiology of the placenta. Placenta 64:S9–15
    [Google Scholar]
  18. 18. 
    Roopenian DC, Akilesh S. 2007. FcRn: The neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7:9715–25
    [Google Scholar]
  19. 19. 
    Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T et al. 2020. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science 367:6481eaaw8429
    [Google Scholar]
  20. 20. 
    Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y et al. 2016. The maternal microbiota drives early postnatal innate immune development. Science 351:62791296–302
    [Google Scholar]
  21. 21. 
    Atladóttir , Thorsen P, Østergaard L, Schendel DE, Lemcke S et al. 2010. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J. Autism Dev. Disord. 40:121423–30
    [Google Scholar]
  22. 22. 
    Kim S, Kim H, Yim YS, Ha S, Atarashi K et al. 2017. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature 549:7673528–32
    [Google Scholar]
  23. 23. 
    Choi GB, Yim YS, Wong H, Kim S, Kim H et al. 2016. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science 351:6276933–39
    [Google Scholar]
  24. 24. 
    Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. 2004. Transfer of inflammatory cytokines across the placenta. Obstet. Gynecol. 103:3546–50
    [Google Scholar]
  25. 25. 
    Baumgarth N. 2017. A Hard(y) look at B-1 cell development and function. J. Immunol. 199:103387–94
    [Google Scholar]
  26. 26. 
    Havran WL, Allison JP. 1988. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 335:6189443–45
    [Google Scholar]
  27. 27. 
    Randall T, Carragher D, Rangel-Moreno J. 2008. Development of secondary lymphoid organs. Annu. Rev. Immunol. 26:627–50
    [Google Scholar]
  28. 28. 
    Torow N, Yu K, Hassani K, Freitag J, Schulz O et al. 2015. Active suppression of intestinal CD4+TCRαβ+ T-lymphocyte maturation during the postnatal period. Nat. Commun. 6:7725
    [Google Scholar]
  29. 29. 
    Chen JW, Rice TA, Bannock JM, Bielecka AA, Strauss JD et al. 2020. Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition. Science 369:6501320–25
    [Google Scholar]
  30. 30. 
    Zhang X, Zhivaki D, Lo-Man R. 2017. Unique aspects of the perinatal immune system. Nat. Rev. Immunol. 17:8495–507
    [Google Scholar]
  31. 31. 
    Li N, van Unen V, Abdelaal T, Guo N, Kasatskaya SA et al. 2019. Memory CD4+ T cells are generated in the human fetal intestine. Nat. Immunol. 20:3301–12
    [Google Scholar]
  32. 32. 
    Park JE, Jardine L, Gottgens B, Teichmann SA, Haniffa M. 2020. Prenatal development of human immunity. Science 368:6491600–3 https://doi.org/10.1126/science.aaz9330
    [Crossref] [Google Scholar]
  33. 33. 
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G et al. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:2611971–75
    [Google Scholar]
  34. 34. 
    Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A et al. 2019. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature 574:117–21
    [Google Scholar]
  35. 35. 
    Charbonneau MR, O'Donnell D, Blanton LV, Totten SM, Davis JCC et al. 2016. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164:5859–71
    [Google Scholar]
  36. 36. 
    Niewiesk S. 2014. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front. Immunol. 5:446
    [Google Scholar]
  37. 37. 
    Caballero-Flores G, Sakamoto K, Zeng MY, Wang Y, Hakim J et al. 2019. Maternal immunization confers protection to the offspring against an attaching and effacing pathogen through delivery of IgG in breast milk. Cell Host Microbe 25:2313–23.e4
    [Google Scholar]
  38. 38. 
    Gopalakrishna KP, Macadangdang BR, Rogers MB, Tometich JT, Firek BA et al. 2019. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants. Nat. Med. 25:71110–15
    [Google Scholar]
  39. 39. 
    Koch MA, Reiner GL, Lugo KA, Kreuk LSM, Stanbery AG et al. 2016. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Cell 165:4827–41
    [Google Scholar]
  40. 40. 
    Rogier EW, Frantz AL, Bruno MEC, Wedlund L, Cohen DA et al. 2014. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. PNAS 111:83074–79
    [Google Scholar]
  41. 41. 
    Ramanan D, Sefik E, Galván-Peña S, Wu M, Yang L et al. 2020. An immunologic mode of multigenerational transmission governs a gut Treg setpoint. Cell 181:61276–90.e13
    [Google Scholar]
  42. 42. 
    Knoop KA, Gustafsson JK, McDonald KG, Kulkarni DH, Coughlin PE et al. 2017. Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria. Sci. Immunol. 2:18eaao1314
    [Google Scholar]
  43. 43. 
    Al Nabhani Z, Dulauroy S, Marques R, Cousu C, Al Bounny S et al. 2019. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity 50:51276–88.e5
    [Google Scholar]
  44. 44. 
    Laouar A. 2020. Maternal leukocytes and infant immune programming during breastfeeding. Trends Immunol. 41:3225–39
    [Google Scholar]
  45. 45. 
    Cabinian A, Sinsimer D, Tang M, Zumba O, Mehta H et al. 2016. Transfer of maternal immune cells by breastfeeding: Maternal cytotoxic T lymphocytes present in breast milk localize in the Peyer's patches of the nursed infant. PLOS ONE 11:6e0156762
    [Google Scholar]
  46. 46. 
    Huda MN, Lewis Z, Kalanetra KM, Rashid M, Ahmad SM et al. 2014. Stool microbiota and vaccine responses of infants. Pediatrics 134:2e362–72
    [Google Scholar]
  47. 47. 
    Huda MN, Ahmad SM, Alam MJ, Khanam A, Kalanetra KM et al. 2019. Bifidobacterium abundance in early infancy and vaccine response at 2 years of age. Pediatrics 143:2e20181489
    [Google Scholar]
  48. 48. 
    Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A et al. 2008. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Gastrointest. Liver Physiol. 295:51025–34
    [Google Scholar]
  49. 49. 
    Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y et al. 2011. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469:7331543–49
    [Google Scholar]
  50. 50. 
    Elahi S, Ertelt JM, Kinder JM, Jiang TT, Zhang X et al. 2013. Immunosuppressive CD71 1 erythroid cells compromise neonatal host defence against infection. Nature 504:7478158–62
    [Google Scholar]
  51. 51. 
    Rudd BD. 2020. Neonatal T cells: a reinterpretation. Annu. Rev. Immunol. 38:229–47
    [Google Scholar]
  52. 52. 
    Thome JJC, Bickham KL, Ohmura Y, Kubota M, Matsuoka N et al. 2016. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nat. Med. 22:172–77
    [Google Scholar]
  53. 53. 
    McGovern N, Shin A, Low G, Low D, Duan K et al. 2017. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature 546:7660662–66
    [Google Scholar]
  54. 54. 
    Scharschmidt TC, Vasquez KS, Truong HA, Gearty SV, Pauli ML et al. 2015. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 43:51011–21
    [Google Scholar]
  55. 55. 
    Gollwitzer ES, Saglani S, Trompette A, Yadava K, Sherburn R et al. 2014. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20:6642–47
    [Google Scholar]
  56. 56. 
    New JS, Dizon BLP, Fucile CF, Rosenberg AF, Kearney JF, King RG. 2020. Neonatal exposure to commensal-bacteria-derived antigens directs polysaccharide-specific B-1 B cell repertoire development. Immunity 53:1172–86.e6
    [Google Scholar]
  57. 57. 
    Godfrey DI, Uldrich AP, Mccluskey J, Rossjohn J, Moody DB. 2015. The burgeoning family of unconventional T cells. Nat. Immunol. 16:111114–23
    [Google Scholar]
  58. 58. 
    Adams EJ, Luoma AM. 2013. The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I–like molecules. Annu. Rev. Immunol. 31:529–61
    [Google Scholar]
  59. 59. 
    McVay LD, Carding SR. 1996. Extrathymic origin of human γδ T cells during fetal development. J. Immunol. 157:72873–82
    [Google Scholar]
  60. 60. 
    Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B et al. 2012. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:7426717–23
    [Google Scholar]
  61. 61. 
    Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y et al. 1997. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278:53431626–29
    [Google Scholar]
  62. 62. 
    Olszak T, An D, Zeissig S, Vera MP, Richter J et al. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:6080489–93
    [Google Scholar]
  63. 63. 
    An D, Oh SF, Olszak T, Neves JF, Avci FY et al. 2014. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156:1–2123–33
    [Google Scholar]
  64. 64. 
    Constantinides MG, Link VM, Tamoutounour S, Wong AC, Perez-Chaparro PJ et al. 2019. MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science 366:6464eaax6624
    [Google Scholar]
  65. 65. 
    Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V et al. 2003. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:6928164–69
    [Google Scholar]
  66. 66. 
    Koay HF, Gherardin NA, Enders A, Loh L, Mackay LK et al. 2016. A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nat. Immunol. 17:111300–11
    [Google Scholar]
  67. 67. 
    Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. 2017. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med. 23:3314–26
    [Google Scholar]
  68. 68. 
    Thaiss CA, Zmora N, Levy M, Elinav E. 2016. The microbiome and innate immunity. Nature 535:761065–74
    [Google Scholar]
  69. 69. 
    Robertson SJ, Goethel A, Girardin SE, Philpott DJ. 2018. Innate immune influences on the gut microbiome: lessons from mouse models. Trends Immunol. 39:12992–1004
    [Google Scholar]
  70. 70. 
    Peterson DA, McNulty NP, Guruge JL, Gordon JI. 2007. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2:5328–39
    [Google Scholar]
  71. 71. 
    Fernandez MI, Pedron T, Tournebize R, Olivo-Marin JC, Sansonetti PJ, Phalipon A. 2003. Anti-inflammatory role for intracellular dimeric immunoglobulin A by neutralization of lipopolysaccharide in epithelial cells. Immunity 18:6739–49
    [Google Scholar]
  72. 72. 
    Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K. 2010. Adaptive immune regulation in the gut: T cell–dependent and T cell–independent IgA synthesis. Annu. Rev. Immunol. 28:243–73
    [Google Scholar]
  73. 73. 
    Van Der Waaij LA, Limburg PC, Mesander G, Van Der Waaij D. 1996. In vivo IgA coating of anaerobic bacteria in human faeces. Gut 38:348–54
    [Google Scholar]
  74. 74. 
    Kramer DR, Cebra JJ. 1995. Early appearance of “natural” mucosal IgA responses and germinal centers in suckling mice developing in the absence of maternal antibodies. J. Immunol. 154:52051–62
    [Google Scholar]
  75. 75. 
    Macpherson AJ, Hunziker L, McCoy K, Lamarre A. 2001. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3:121021–35
    [Google Scholar]
  76. 76. 
    Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM. 2000. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288:54742222–26
    [Google Scholar]
  77. 77. 
    Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. 2002. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:55971424–27
    [Google Scholar]
  78. 78. 
    Macpherson AJ, Uhr T. 2004. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303:56641662–65
    [Google Scholar]
  79. 79. 
    Fagarasan S, Kinoshita K, Muramatsu M, Ikuta K, Honjo T. 2001. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413:6856639–43
    [Google Scholar]
  80. 80. 
    Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG. 2016. IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches. Science 352:6287aaf4822
    [Google Scholar]
  81. 81. 
    Bunker JJ, Erickson SA, Flynn TM, Henry C, Koval JC et al. 2017. Natural polyreactive IgA antibodies coat the intestinal microbiota. Science 358:6361eaan6619
    [Google Scholar]
  82. 82. 
    Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A et al. 2002. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3:9822–29
    [Google Scholar]
  83. 83. 
    He B, Xu W, Santini PA, Polydorides AD, Chiu A et al. 2007. Intestinal bacteria trigger T cell-independent immunoglobulin A2 class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26:6812–26
    [Google Scholar]
  84. 84. 
    Mora JR, Iwata M, Eksteen B, Song SY, Junt T et al. 2006. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:58021157–60
    [Google Scholar]
  85. 85. 
    Cazac BB, Roes J. 2000. TGF-β receptor controls B cell responsiveness and induction of IgA in vivo. Immunity 13:4443–51
    [Google Scholar]
  86. 86. 
    Grootjans J, Krupka N, Hosomi S, Matute JD, Hanley T et al. 2019. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response. Science 363:6430993–98
    [Google Scholar]
  87. 87. 
    Macpherson AJ, Yilmaz B, Limenitakis JP, Ganal-Vonarburg SC. 2018. IgA function in relation to the intestinal microbiota. Annu. Rev. Immunol. 36:359–81
    [Google Scholar]
  88. 88. 
    Bunker JJ, Flynn TM, Koval JC, Shaw DG, Meisel M et al. 2015. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A. Immunity 43:3541–53
    [Google Scholar]
  89. 89. 
    Bunker JJ, Bendelac A. 2018. IgA responses to microbiota. Immunity 49:2211–24
    [Google Scholar]
  90. 90. 
    Ansaldo E, Slayden LC, Ching KL, Koch MA, Wolf NK et al. 2019. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science 364:64461179–84
    [Google Scholar]
  91. 91. 
    Palm NW, De Zoete MR, Cullen TW, Barry NA, Stefanowski J et al. 2014. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158:51000–10
    [Google Scholar]
  92. 92. 
    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. Nat. Immunol. 12:3264–70
    [Google Scholar]
  93. 93. 
    Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T et al. 2015. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci. Transl. Med. 7:276276ra24
    [Google Scholar]
  94. 94. 
    Hapfelmeier S, Lawson MAE, Slack E, Kirundi JK, Stoel M et al. 2010. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328:59861705–9
    [Google Scholar]
  95. 95. 
    Li H, Limenitakis JP, Greiff V, Yilmaz B, Schären O et al. 2020. Mucosal or systemic microbiota exposures shape the B cell repertoire. Nature 584:7820274–78
    [Google Scholar]
  96. 96. 
    Yel L. 2010. Selective IgA deficiency. J. Clin. Immunol. 30:10–16
    [Google Scholar]
  97. 97. 
    Chen K, Magri G, Grasset EK, Cerutti A. 2020. Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA. Nat. Rev. Immunol. 20:7427–41
    [Google Scholar]
  98. 98. 
    Benckert J, Schmolka N, Kreschel C, Zoller MJ, Sturm A et al. 2011. The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J. Clin. Investig. 121:51946–55
    [Google Scholar]
  99. 99. 
    Magri G, Comerma L, Pybus M, Sintes J, Lligé D et al. 2017. Human secretory IgM emerges from plasma cells clonally related to gut memory B cells and targets highly diverse commensals. Immunity 47:1118–34.e8
    [Google Scholar]
  100. 100. 
    Slack E, Hapfelmeier S, Stecher B, Velykoredko Y, Stoel M et al. 2009. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325:5940617–20
    [Google Scholar]
  101. 101. 
    Zeng MY, Cisalpino D, Varadarajan S, Hellman J, Warren HS et al. 2016. Gut microbiota-induced immunoglobulin G controls systemic infection by symbiotic bacteria and pathogens. Immunity 44:3647–58
    [Google Scholar]
  102. 102. 
    Xu Z, Takizawa F, Casadei E, Shibasaki Y, Ding Y et al. 2020. Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution. Sci. Immunol. 5:44eaay3254
    [Google Scholar]
  103. 103. 
    Stappenbeck TS, Virgin HW. 2016. Accounting for reciprocal host-microbiome interactions in experimental science. Nature 534:7606191–99
    [Google Scholar]
  104. 104. 
    Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y et al. 2012. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 336:6080485–89
    [Google Scholar]
  105. 105. 
    Fransen F, Zagato E, Mazzini E, Fosso B, Manzari C et al. 2015. BALB/c and C57BL/6 mice differ in polyreactive IgA abundance, which impacts the generation of antigen-specific IgA and microbiota diversity. Immunity 43:3527–40
    [Google Scholar]
  106. 106. 
    Donaldson GP, Ladinsky MS, Yu KB, Sanders JG, Yoo BB et al. 2018. Gut microbiota utilize immunoglobulin A for mucosal colonization. Science 360:6390795–800
    [Google Scholar]
  107. 107. 
    Moor K, Diard M, Sellin ME, Felmy B, Wotzka SY et al. 2017. High-avidity IgA protects the intestine by enchaining growing bacteria. Nature 544:7651498–502
    [Google Scholar]
  108. 108. 
    Cullender TC, Chassaing B, Janzon A, Kumar K, Muller CE et al. 2013. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14:5571–81
    [Google Scholar]
  109. 109. 
    Cong Y, Feng T, Fujihashi K, Schoeb TR, Elson CO 2009. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. PNAS 106:4619256–61
    [Google Scholar]
  110. 110. 
    Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagán AJ et al. 2012. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337:61011553–56
    [Google Scholar]
  111. 111. 
    Wilmore JR, Gaudette BT, Gomez Atria D, Hashemi T, Jones DD et al. 2018. Commensal microbes induce serum IgA responses that protect against polymicrobial sepsis. Cell Host Microbe 23:3302–11.e3
    [Google Scholar]
  112. 112. 
    Castro-Dopico T, Dennison TW, Ferdinand JR, Mathews RJ, Fleming A et al. 2019. Anti-commensal IgG drives intestinal inflammation and type 17 immunity in ulcerative colitis. Immunity 50:41099–114.e10
    [Google Scholar]
  113. 113. 
    Metz D, Jurecka W, Gebhart W, Schmidt J, Mainitz M, Niebauer G. 1989. Immunohistochemical demonstration of immunoglobulin A in human sebaceous and sweat glands. J. Investig. Dermatol. 92:113–17
    [Google Scholar]
  114. 114. 
    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 118:2229–41
    [Google Scholar]
  115. 115. 
    Macleod AS, Hemmers S, Garijo O, Chabod M, Mowen K et al. 2013. Dendritic epidermal T cells regulate skin antimicrobial barrier function. J. Clin. Investig. 123:104364–74
    [Google Scholar]
  116. 116. 
    Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R 2002. Protection of the intestinal mucosa by intraepithelial γδ T cells. PNAS 99:2214338–43
    [Google Scholar]
  117. 117. 
    Leng T, Akther HD, Hackstein CP, Powell K, King T et al. 2019. TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions. Cell Rep 28:123077–91.e5
    [Google Scholar]
  118. 118. 
    Li J, Reantragoon R, Kostenko L, Corbett AJ, Varigos G, Carbone FR. 2017. The frequency of mucosal-associated invariant T cells is selectively increased in dermatitis herpetiformis. Australas. J. Dermatol. 58:3200–4
    [Google Scholar]
  119. 119. 
    Naik S, Bouladoux N, Linehan JL, Han S-J, Harrison OJ et al. 2015. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520:7545104–8
    [Google Scholar]
  120. 120. 
    Linehan JL, Harrison OJ, Han SJ, Byrd AL, Vujkovic-Cvijin I et al. 2018. Non-classical immunity controls microbiota impact on skin immunity and tissue repair. Cell 172:4784–96.e18
    [Google Scholar]
  121. 121. 
    Harrison OJ, Linehan JL, Shih HY, Bouladoux N, Han SJ et al. 2019. Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science 363:6422eaat6280
    [Google Scholar]
  122. 122. 
    Ismail AS, Behrendt CL, Hooper LV. 2009. Reciprocal interactions between commensal bacteria and γδ intraepithelial lymphocytes during mucosal injury. J. Immunol. 182:53047–54
    [Google Scholar]
  123. 123. 
    Ismail AS, Severson KM, Vaishnava S, Behrendt CL, Yu X et al. 2011. γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. PNAS 108:218743–48
    [Google Scholar]
  124. 124. 
    Hoytema van Konijnenburg DP, Reis BS, Pedicord VA, Farache J, Victora GD, Mucida D. 2017. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell 171:4783–94.e13
    [Google Scholar]
  125. 125. 
    Nieuwenhuis EES, Matsumoto T, Lindenbergh D, Willemsen R, Kaser A et al. 2009. Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J. Clin. Investig. 119:51241–50
    [Google Scholar]
  126. 126. 
    St. Leger AJ, Desai JV, Drummond RA, Kugadas A, Almaghrabi F et al. 2017. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal γδ T cells. Immunity 47:1148–58.e5
    [Google Scholar]
  127. 127. 
    Ridaura VK, Bouladoux N, Claesen J, Chen YE, Byrd AL et al. 2018. Contextual control of skin immunity and inflammation by Corynebacterium. J. Exp. Med. 215:3785–99
    [Google Scholar]
  128. 128. 
    De Libero G, Lau S-Y, Mori L. 2015. Phosphoantigen presentation to TCR γδ cells, a conundrum getting less gray zones. Front. Immunol. 5:679
    [Google Scholar]
  129. 129. 
    Dias J, Leeansyah E, Sandberg JK 2017. Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines. PNAS 114:27E5434–43
    [Google Scholar]
  130. 130. 
    Howson LJ, Awad W, von Borstel A, Jing Lim H, McWilliam HEG et al. 2020. Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1. Sci. Immunol. 5:49eabc9492
    [Google Scholar]
  131. 131. 
    Hegazy AN, West NR, Stubbington MJT, Wendt E, Suijker KIM et al. 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 153:51320–37.e16
    [Google Scholar]
  132. 132. 
    Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A et al. 2009. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31:4677–89
    [Google Scholar]
  133. 133. 
    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:3485–98
    [Google Scholar]
  134. 134. 
    Talham GL, Jiang HQ, Bos NA, Cebra JJ. 1999. Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infect. Immun. 67:41992–2000
    [Google Scholar]
  135. 135. 
    Umesaki Y, Setoyama H, Matsumoto S, Imaoka A, Itoh K. 1999. Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect. Immun. 67:73504–11
    [Google Scholar]
  136. 136. 
    Yang Y, Torchinsky MB, Gobert M, Xiong H, Xu M et al. 2014. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510:7503152–56
    [Google Scholar]
  137. 137. 
    Lee YK, Menezes JS, Umesaki Y, Mazmanian SK 2011. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. PNAS 108:Suppl. 14615–22
    [Google Scholar]
  138. 138. 
    Wu HJ, Ivanov II, Darce J, Hattori K, Shima T et al. 2010. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:6815–27
    [Google Scholar]
  139. 139. 
    Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X et al. 2011. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334:6053255–58
    [Google Scholar]
  140. 140. 
    Ivanov II, Frutos RDL, Manel N, Yoshinaga K, Rifkin DB et al. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4:4337–49
    [Google Scholar]
  141. 141. 
    Sczesnak A, Segata N, Qin X, Gevers D, Petrosino JF et al. 2011. The genome of Th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment. Cell Host Microbe 10:3260–72
    [Google Scholar]
  142. 142. 
    Atarashi K, Tanoue T, Ando M, Kamada N. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:2367–80
    [Google Scholar]
  143. 143. 
    Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan TG et al. 2017. Mining the human gut microbiota for immunomodulatory organisms. Cell 168:5928–43.e11
    [Google Scholar]
  144. 144. 
    Tan TG, Sefik E, Geva-Zatorsky N, Kua L, Naskar D et al. 2016. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. PNAS 113:50E8141–50
    [Google Scholar]
  145. 145. 
    Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W et al. 2019. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565:7741600–5
    [Google Scholar]
  146. 146. 
    Byrd AL, Deming C, Cassidy SKB, Harrison OJ, Ng WI et al. 2017. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci. Transl. Med. 9:397eaal4651
    [Google Scholar]
  147. 147. 
    Hurabielle C, Link VM, Bouladoux N, Han SJ, Merrill ED et al. 2020. Immunity to commensal skin fungi promotes psoriasiform skin inflammation. PNAS 117:2816465–74
    [Google Scholar]
  148. 148. 
    Chen YE, Fischbach MA, Belkaid Y. 2018. Skin microbiota-host interactions. Nature 553:7689427–36 Erratum. 2018. Nature 555(7697):543
    [Google Scholar]
  149. 149. 
    Di Domizio J, Belkhodja C, Chenuet P, Fries A, Murray T et al. 2020. The commensal skin microbiota triggers type I IFN-dependent innate repair responses in injured skin. Nat. Immunol. 21:91034–45
    [Google Scholar]
  150. 150. 
    Lai Y, Di Nardo A, Nakatsuji T, Leichtle A, Yang Y et al. 2009. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat. Med. 15:121377–82
    [Google Scholar]
  151. 151. 
    Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337:60981115–19
    [Google Scholar]
  152. 152. 
    Sano T, Huang W, Hall JA, Yang Y, Chen A et al. 2015. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163:2381–93
    [Google Scholar]
  153. 153. 
    Derebe MG, Zlatkov CM, Gattu S, Ruhn KA, Vaishnava S et al. 2014. Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection. eLife 3:e03206
    [Google Scholar]
  154. 154. 
    Tamoutounour S, Han SJ, Deckers J, Constantinides MG, Hurabielle C et al. 2019. Keratinocyte-intrinsic MHCII expression controls microbiota-induced Th1 cell responses. PNAS 116:4723643–52
    [Google Scholar]
  155. 155. 
    Bilate AM, London M, Castro TBR, Mesin L, Bortolatto J et al. 2020. T cell receptor is required for differentiation, but not maintenance, of intestinal CD4+ intraepithelial lymphocytes. Immunity 53:51001–14.e20
    [Google Scholar]
  156. 156. 
    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS 110:229066–71
    [Google Scholar]
  157. 157. 
    Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT et al. 2018. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359:637191–97
    [Google Scholar]
  158. 158. 
    Xu M, Pokrovskii M, Ding Y, Yi R, Au C et al. 2018. C-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554:7692373–77
    [Google Scholar]
  159. 159. 
    Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ et al. 2006. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203:112473–83
    [Google Scholar]
  160. 160. 
    Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL et al. 2006. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203:112485–94
    [Google Scholar]
  161. 161. 
    Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F. 2003. CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197:1111–19
    [Google Scholar]
  162. 162. 
    Lee JY, Hall JA, Kroehling L, Wu L, Najar T et al. 2020. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell 180:179–91.e16
    [Google Scholar]
  163. 163. 
    Mackay LK, Stock AT, Ma JZ, Jones CM, Kent SJ et al. 2012. Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. PNAS 109:187037–42
    [Google Scholar]
  164. 164. 
    Homann D, Teyton L, Oldstone MBA. 2001. Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory. Nat. Med. 7:8913–19
    [Google Scholar]
  165. 165. 
    Friedrich M, Pohin M, Powrie F. 2019. Cytokine networks in the pathophysiology of inflammatory bowel disease. Immunity 50:4992–1006
    [Google Scholar]
  166. 166. 
    Whibley N, Tucci A, Powrie F. 2019. Regulatory T cell adaptation in the intestine and skin. Nat. Immunol. 20:4386–96
    [Google Scholar]
  167. 167. 
    Coombes JL, Siddiqui KRR, Arancibia-Cárcamo CV, Hall J, Sun CM et al. 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism. J. Exp. Med. 204:81757–64
    [Google Scholar]
  168. 168. 
    Esterházy D, Canesso MCC, Mesin L, Muller PA, de Castro TBR et al. 2019. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature 569:7754126–30
    [Google Scholar]
  169. 169. 
    Mucida D, Kutchukhidze N, Erazo A, Russo M, Lafaille JJ, Curotto De Lafaille MA. 2005. Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Investig. 115:71923–33
    [Google Scholar]
  170. 170. 
    Mucida D, Park Y, Kim G, Turovskaya O, Scott I et al. 2007. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:5835256–60
    [Google Scholar]
  171. 171. 
    Wannemuehler MJ, Kiyono H, Babb JL, Michalek SM, McGhee JR. 1982. Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germfree mice to sensitivity to oral tolerance induction. J. Immunol. 129:3959–65
    [Google Scholar]
  172. 172. 
    Geuking MB, Cahenzli J, Lawson MAE, Ng DCK, Slack E et al. 2011. Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34:5794–806
    [Google Scholar]
  173. 173. 
    Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K et al. 2015. The microbiota regulates type 2 immunity through RORγt+ T cells. Science 349:6251989–93
    [Google Scholar]
  174. 174. 
    Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D et al. 2015. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 349:6251993–97
    [Google Scholar]
  175. 175. 
    Yang BH, Hagemann S, Mamareli P, Lauer U, Hoffmann U et al. 2016. Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol 9:2444–57
    [Google Scholar]
  176. 176. 
    Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio C-W et al. 2011. Peripheral education of the immune system by colonic commensal microbiota. Nature 478:7368250–54
    [Google Scholar]
  177. 177. 
    Nutsch K, Chai JN, Ai TL, Russler-Germain E, Feehley T et al. 2016. Rapid and efficient generation of regulatory T cells to commensal antigens in the periphery. Cell Rep 17:1206–20
    [Google Scholar]
  178. 178. 
    Faith JJ, Ahern PP, Ridaura VK, Cheng J, Gordon JI. 2014. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci. Transl. Med. 6:220220ra11
    [Google Scholar]
  179. 179. 
    Britton GJ, Contijoch EJ, Mogno I, Vennaro OH, Llewellyn SR et al. 2019. Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and RORγt+ regulatory T cells and exacerbate colitis in mice. Immunity 50:1212–24.e4
    [Google Scholar]
  180. 180. 
    Izcue A, Coombes JL, Powrie F. 2006. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol. Rev. 212:256–71
    [Google Scholar]
  181. 181. 
    Sujino T, London M, Van Konijnenburg DPH, Rendon T, Buch T et al. 2016. Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation. Science 352:62931581–86
    [Google Scholar]
  182. 182. 
    Wohlfert EA, Grainger JR, Bouladoux N, Konkel JE, Oldenhove G et al. 2011. GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. J. Clin. Investig. 121:114503–15
    [Google Scholar]
  183. 183. 
    Neumann C, Blume J, Roy U, Teh PP, Vasanthakumar A et al. 2019. c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis. Nat. Immunol. 20:4471–81
    [Google Scholar]
  184. 184. 
    Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:7480451–55
    [Google Scholar]
  185. 185. 
    Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50
    [Google Scholar]
  186. 186. 
    Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73
    [Google Scholar]
  187. 187. 
    Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–41
    [Google Scholar]
  188. 188. 
    Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y et al. 2013. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500:7461232–36
    [Google Scholar]
  189. 189. 
    Narushima S, Sugiura Y, Oshima K, Atarashi K, Hattori M et al. 2014. Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut Microbes 5:3333–39
    [Google Scholar]
  190. 190. 
    Campbell C, McKenney PT, Konstantinovsky D, Isaeva OI, Schizas M et al. 2020. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature 581:7809475–79
    [Google Scholar]
  191. 191. 
    Hang S, Paik D, Yao L, Kim E, Jamma T et al. 2019. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576:7785143–48 Erratum. 2020. Nature 579:E7
    [Google Scholar]
  192. 192. 
    Song X, Sun X, Oh SF, Wu M, Zhang Y et al. 2020. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature 577:7790410–15
    [Google Scholar]
  193. 193. 
    Verma R, Lee C, Jeun EJ, Yi J, Kim KS et al. 2018. Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3+ regulatory T cells. Sci. Immunol. 3:28eaat6975
    [Google Scholar]
  194. 194. 
    Mazmanian SK, Cui HL, Tzianabos AO, Kasper DL. 2005. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:1107–18
    [Google Scholar]
  195. 195. 
    Mazmanian SK, Round JL, Kasper DL. 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:7195620–25
    [Google Scholar]
  196. 196. 
    Leech JM, Dhariwala MO, Lowe MM, Chu K, Merana GR et al. 2019. Toxin-triggered interleukin-1 receptor signaling enables early-life discrimination of pathogenic versus commensal skin bacteria. Cell Host Microbe 26:6795–809.e5
    [Google Scholar]
  197. 197. 
    Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP et al. 2014. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:61781249288
    [Google Scholar]
  198. 198. 
    Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH et al. 2013. Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat. Med. 19:6713–21
    [Google Scholar]
  199. 199. 
    Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F et al. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:72681282–86
    [Google Scholar]
  200. 200. 
    Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN et al. 2012. Interactions between commensal fungi and the C-type lectin receptor dectin-1 influence colitis. Science 336:60861314–17
    [Google Scholar]
  201. 201. 
    Rohlke F, Stollman N. 2012. Fecal microbiota transplantation in relapsing Clostridium difficile infection. Therap. Adv. Gastroenterol. 5:6403–20
    [Google Scholar]
  202. 202. 
    Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L et al. 2017. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature 548:7668407–12
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-093019-112348
Loading
/content/journals/10.1146/annurev-immunol-093019-112348
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error