Homeostatic Immunity and the Microbiota

Immunity

Volumn 46, Issue 4, 2017, Pages 562-576

  Belkaid, Yasmine ^a   Harrison, Oliver J ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TUMOR VACCINE;

ADAPTIVE IMMUNITY; CANCER IMMUNOTHERAPY; HEMATOPOIESIS; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; IMMUNITY; IMMUNOREACTIVITY; INFECTION; INNATE IMMUNITY; LYMPHOCYTE; MICROFLORA; NONHUMAN; PRIORITY JOURNAL; REVIEW; VACCINATION; ANIMAL; BIOLOGICAL MODEL; HOST PATHOGEN INTERACTION; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; MICROBIOLOGY; PHYSIOLOGY;

ADAPTIVE IMMUNITY; ANIMALS; HOMEOSTASIS; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE SYSTEM; IMMUNE TOLERANCE; IMMUNITY, INNATE; MICROBIOTA; MODELS, IMMUNOLOGICAL;

EID: 85019031108     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2017.04.008     Document Type: Review

References (196)

1. Abt, M.C., Osborne, L.C., Monticelli, L.A., Doering, T.A., Alenghat, T., Sonnenberg, G.F., Paley, M.A., Antenus, M., Williams, K.L., Erikson, J., et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37 (2012), 158–170.
2. Adams, E.J., Luoma, A.M., The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules. Annu. Rev. Immunol. 31 (2013), 529–561.
3. 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., Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156 (2014), 123–133.
4. 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., Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504 (2013), 451–455.
5. Arrieta, M.C., Stiemsma, L.T., Amenyogbe, N., Brown, E.M., Finlay, B., The intestinal microbiome in early life: health and disease. Front. Immunol., 5, 2014, 427.
6. Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., Takeda, K., ATP drives lamina propria T(H)17 cell differentiation. Nature 455 (2008), 808–812.
7. Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331 (2011), 337–341.
8. Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 (2013), 232–236.
9. Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., et al. Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Cell 163 (2015), 367–380.
10. Bain, C.C., Bravo-Blas, A., Scott, C.L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L.C., Artis, D., Mowat, A.M., Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15 (2014), 929–937.
11. Balmer, M.L., Schürch, C.M., Saito, Y., Geuking, M.B., Li, H., Cuenca, M., Kovtonyuk, L.V., McCoy, K.D., Hapfelmeier, S., Ochsenbein, A.F., et al. Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling. J. Immunol. 193 (2014), 5273–5283.
12. Balmer, M.L., Slack, E., de Gottardi, A., Lawson, M.A., Hapfelmeier, S., Miele, L., Grieco, A., Van Vlierberghe, H., Fahrner, R., Patuto, N., et al. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci. Transl. Med., 6, 2014, 237ra66.
13. Belkaid, Y., Naik, S., Compartmentalized and systemic control of tissue immunity by commensals. Nat. Immunol. 14 (2013), 646–653.
14. Belkaid, Y., Piccirillo, C.A., Mendez, S., Shevach, E.M., Sacks, D.L., CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420 (2002), 502–507.
15. Blekhman, R., Goodrich, J.K., Huang, K., Sun, Q., Bukowski, R., Bell, J.T., Spector, T.D., Keinan, A., Ley, R.E., Gevers, D., Clark, A.G., Host genetic variation impacts microbiome composition across human body sites. Genome Biol., 16, 2015, 191.
16. Blumberg, R., Powrie, F., Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med., 4, 2012, 137rv7.
17. Boullier, S., Tanguy, M., Kadaoui, K.A., Caubet, C., Sansonetti, P., Corthésy, B., Phalipon, A., Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits. J. Immunol. 183 (2009), 5879–5885.
18. Brandl, K., Plitas, G., Schnabl, B., DeMatteo, R.P., Pamer, E.G., MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J. Exp. Med. 204 (2007), 1891–1900.
19. Buffie, C.G., Pamer, E.G., Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13 (2013), 790–801.
20. Buffie, C.G., Bucci, V., Stein, R.R., McKenney, P.T., Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew, M., Viale, A., et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517 (2015), 205–208.
21. Cash, H.L., Whitham, C.V., Behrendt, C.L., Hooper, L.V., Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313 (2006), 1126–1130.
22. Cebra, J.J., Influences of microbiota on intestinal immune system development. Am. J. Clin. Nutr. 69 (1999), 1046S–1051S.
23. Cebula, A., Seweryn, M., Rempala, G.A., Pabla, S.S., McIndoe, R.A., Denning, T.L., Bry, L., Kraj, P., Kisielow, P., Ignatowicz, L., Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature 497 (2013), 258–262.
24. Chang, P.V., Hao, L., Offermanns, S., Medzhitov, R., The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 111 (2014), 2247–2252.
25. Chieppa, M., Rescigno, M., Huang, A.Y., Germain, R.N., Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203 (2006), 2841–2852.
26. Chudnovskiy, A., Mortha, A., Kana, V., Kennard, A., Ramirez, J.D., Rahman, A., Remark, R., Mogno, I., Ng, R., Gnjatic, S., et al. Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome. Cell, 167, 2016 444-456 e414.
27. Clarke, T.B., Davis, K.M., Lysenko, E.S., Zhou, A.Y., Yu, Y., Weiser, J.N., Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16 (2010), 228–231.
28. Cong, Y., Feng, T., Fujihashi, K., Schoeb, T.R., Elson, C.O., A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc. Natl. Acad. Sci. USA 106 (2009), 19256–19261.
29. Coombes, J.L., Siddiqui, K.R., Arancibia-Carcamo, C.V., Hall, J., Sun, C.M., Belkaid, Y., Powrie, F., A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-{beta}- and retinoic acid-dependent mechanism. J Exp Med, 204, 2007 1757-64.
30. Cui, G., Staron, M.M., Gray, S.M., Ho, P.C., Amezquita, R.A., Wu, J., Kaech, S.M., IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity. Cell 161 (2015), 750–761.
31. Cummings, J.H., Pomare, E.W., Branch, W.J., Naylor, C.P., Macfarlane, G.T., Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28 (1987), 1221–1227.
32. Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., Duong, C.P., Flament, C., Lepage, P., Roberti, M.P., et al. Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects. Immunity 45 (2016), 931–943.
33. Derebe, M.G., Zlatkov, C.M., Gattu, S., Ruhn, K.A., Vaishnava, S., Diehl, G.E., MacMillan, J.B., Williams, N.S., Hooper, L.V., Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection. eLife, 3, 2014, e03206.
34. Deshmukh, H.S., Liu, Y., Menkiti, O.R., Mei, J., Dai, N., O'Leary, C.E., Oliver, P.M., Kolls, J.K., Weiser, J.N., Worthen, G.S., The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat. Med. 20 (2014), 524–530.
35. Donia, M.S., Fischbach, M.A., HUMAN MICROBIOTA. Small molecules from the human microbiota. Science, 349, 2015, 1254766.
36. Duan, J., Chung, H., Troy, E., Kasper, D.L., Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells. Cell Host Microbe 7 (2010), 140–150.
37. 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., NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145 (2011), 745–757.
38. Eloe-Fadrosh, E.A., McArthur, M.A., Seekatz, A.M., Drabek, E.F., Rasko, D.A., Sztein, M.B., Fraser, C.M., Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses. PLoS ONE, 8, 2013, e62026.
39. Esterházy, D., Loschko, J., London, M., Jove, V., Oliveira, T.Y., Mucida, D., Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance. Nat. Immunol. 17 (2016), 545–555.
40. Faith, J.J., Ahern, P.P., Ridaura, V.K., Cheng, J., Gordon, J.I., Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci. Transl. Med., 6, 2014, 220ra11.
41. Fernandez, M.I., Pedron, T., Tournebize, R., Olivo-Marin, J.C., Sansonetti, P.J., Phalipon, A., Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells. Immunity 18 (2003), 739–749.
42. Fink, L.N., Metzdorff, S.B., Zeuthen, L.H., Nellemann, C., Kristensen, M.B., Licht, T.R., Frøkiær, H., Establishment of tolerance to commensal bacteria requires a complex microbiota and is accompanied by decreased intestinal chemokine expression. Am. J. Physiol. Gastrointest. Liver Physiol. 302 (2012), G55–G65.
43. Franchi, L., Kamada, N., Nakamura, Y., Burberry, A., Kuffa, P., Suzuki, S., Shaw, M.H., Kim, Y.G., Núñez, G., NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol. 13 (2012), 449–456.
44. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504 (2013), 446–450.
45. Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31 (2009), 677–689.
46. Gensollen, T., Iyer, S.S., Kasper, D.L., Blumberg, R.S., How colonization by microbiota in early life shapes the immune system. Science 352 (2016), 539–544.
47. Gerbe, F., Sidot, E., Smyth, D.J., Ohmoto, M., Matsumoto, I., Dardalhon, V., Cesses, P., Garnier, L., Pouzolles, M., Brulin, B., et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529 (2016), 226–230.
48. Geuking, M.B., Cahenzli, J., Lawson, M.A., Ng, D.C., Slack, E., Hapfelmeier, S., McCoy, K.D., Macpherson, A.J., Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34 (2011), 794–806.
49. Gomez de Agüero, M., Ganal-Vonarburg, S.C., Fuhrer, T., Rupp, S., Uchimura, Y., Li, H., Steinert, A., Heikenwalder, M., Hapfelmeier, S., Sauer, U., et al. The maternal microbiota drives early postnatal innate immune development. Science 351 (2016), 1296–1302.
50. Goodrich, J.K., Waters, J.L., Poole, A.C., Sutter, J.L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J.T., et al. Human genetics shape the gut microbiome. Cell 159 (2014), 789–799.
51. Goris, H., de Boer, F., van der Waaij, D., Myelopoiesis in experimentally contaminated specific-pathogen-free and germfree mice during oral administration of polymyxin. Infect. Immun. 50 (1985), 437–441.
52. Grainger, J.R., Wohlfert, E.A., Fuss, I.J., Bouladoux, N., Askenase, M.H., Legrand, F., Koo, L.Y., Brenchley, J.M., Fraser, I.D., Belkaid, Y., Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat. Med. 19 (2013), 713–721.
53. Gray, E.E., Suzuki, K., Cyster, J.G., Cutting edge: Identification of a motile IL-17-producing gammadelta T cell population in the dermis. J. Immunol. 186 (2011), 6091–6095.
54. Gupta, N., Limbago, B.M., Patel, J.B., Kallen, A.J., Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin. Infect. Dis. 53 (2011), 60–67.
55. 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., et al. The Spectrum and Regulatory Landscape of Intestinal Innate Lymphoid Cells Are Shaped by the Microbiome. Cell, 166, 2016 1231-1246 e1213.
56. Hall, J.A., Bouladoux, N., Sun, C.M., Wohlfert, E.A., Blank, R.B., Zhu, Q., Grigg, M.E., Berzofsky, J.A., Belkaid, Y., Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29 (2008), 637–649.
57. Hand, T.W., Dos Santos, L.M., Bouladoux, N., Molloy, M.J., Pagán, A.J., Pepper, M., Maynard, C.L., Elson, C.O. 3rd, Belkaid, Y., Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337 (2012), 1553–1556.
58. Hapfelmeier, S., Lawson, M.A., Slack, E., Kirundi, J.K., Stoel, M., Heikenwalder, M., Cahenzli, J., Velykoredko, Y., Balmer, M.L., Endt, K., et al. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328 (2010), 1705–1709.
59. Haynes, N.M., Allen, C.D., Lesley, R., Ansel, K.M., Killeen, N., Cyster, J.G., Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J. Immunol. 179 (2007), 5099–5108.
60. Hepworth, M.R., Monticelli, L.A., Fung, T.C., Ziegler, C.G., Grunberg, S., Sinha, R., Mantegazza, A.R., Ma, H.L., Crawford, A., Angelosanto, J.M., et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498 (2013), 113–117.
61. + T cells. Science 348 (2015), 1031–1035.
62. Hill, D.A., Siracusa, M.C., Abt, M.C., Kim, B.S., Kobuley, D., Kubo, M., Kambayashi, T., Larosa, D.F., Renner, E.D., Orange, J.S., et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat. Med. 18 (2012), 538–546.
63. Hirota, K., Turner, J.E., Villa, M., Duarte, J.H., Demengeot, J., Steinmetz, O.M., Stockinger, B., Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol. 14 (2013), 372–379.
64. Hooper, L.V., Macpherson, A.J., Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10 (2010), 159–169.
65. Hornquist, E., Lycke, N., Cholera toxin increases T lymphocyte responses to unrelated antigens. Adv. Exp. Med. Biol. 371B (1995), 1507–1512.
66. Howitt, M.R., Lavoie, S., Michaud, M., Blum, A.M., Tran, S.V., Weinstock, J.V., Gallini, C.A., Redding, K., Margolskee, R.F., Osborne, L.C., et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351 (2016), 1329–1333.
67. Iida, N., Dzutsev, A., Stewart, C.A., Smith, L., Bouladoux, N., Weingarten, R.A., Molina, D.A., Salcedo, R., Back, T., Cramer, S., et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342 (2013), 967–970.
68. Iliev, I.D., Funari, V.A., Taylor, K.D., Nguyen, Q., Reyes, C.N., Strom, S.P., Brown, J., Becker, C.A., Fleshner, P.R., Dubinsky, M., et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336 (2012), 1314–1317.
69. 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., Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. Proc. Natl. Acad. Sci. USA 108 (2011), 8743–8748.
70. Ivanov, I.I., Frutos, Rde.L., Manel, N., Yoshinaga, K., Rifkin, D.B., Sartor, R.B., Finlay, B.B., Littman, D.R., Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4 (2008), 337–349.
71. 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., et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139 (2009), 485–498.
72. Iwamura, C., Bouladoux, N., Belkaid, Y., Sher, A., Jankovic, D., Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis. Blood 129 (2017), 171–176.
73. Jeffries, T.L. Jr., Sacha, C.R., Pollara, J., Himes, J., Jaeger, F.H., Dennison, S.M., McGuire, E., Kunz, E., Eudailey, J.A., Trama, A.M., et al. The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol. 9 (2016), 414–427.
74. Jiang, W., Wang, X., Zeng, B., Liu, L., Tardivel, A., Wei, H., Han, J., MacDonald, H.R., Tschopp, J., Tian, Z., Zhou, R., Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes. J. Exp. Med. 210 (2013), 2465–2476.
75. Josefowicz, S.Z., Niec, R.E., Kim, H.Y., Treuting, P., Chinen, T., Zheng, Y., Umetsu, D.T., Rudensky, A.Y., Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482 (2012), 395–399.
76. Kabelitz, D., Déchanet-Merville, J., Editorial: “Recent Advances in Gamma/Delta T Cell Biology: New Ligands, New Functions, and New Translational Perspectives”. Front. Immunol., 6, 2015, 371.
77. Kawamoto, S., Maruya, M., Kato, L.M., Suda, W., Atarashi, K., Doi, Y., Tsutsui, Y., Qin, H., Honda, K., Okada, T., et al. Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41 (2014), 152–165.
78. Kernbauer, E., Ding, Y., Cadwell, K., An enteric virus can replace the beneficial function of commensal bacteria. Nature 516 (2014), 94–98.
79. Khosravi, A., Yáñez, A., Price, J.G., Chow, A., Merad, M., Goodridge, H.S., Mazmanian, S.K., Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15 (2014), 374–381.
80. Kilian, E., Valentina, D., Andrea, C., IL-17 and IL-22 in immunity: driving protection and pathology. Eur. J. Immunol, 2017, 10.1002/eji.201646723 Published Mar 15, 2017.
81. 2. Cell Host Microbe 15 (2014), 95–102.
82. Kim, K.S., Hong, S.W., Han, D., Yi, J., Jung, J., Yang, B.G., Lee, J.Y., Lee, M., Surh, C.D., Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351 (2016), 858–863.
83. Kinnebrew, M.A., Buffie, C.G., Diehl, G.E., Zenewicz, L.A., Leiner, I., Hohl, T.M., Flavell, R.A., Littman, D.R., Pamer, E.G., Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36 (2012), 276–287.
84. Kiss, E.A., Vonarbourg, C., Kopfmann, S., Hobeika, E., Finke, D., Esser, C., Diefenbach, A., Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334 (2011), 1561–1565.
85. Kiyono, H., McGhee, J.R., Wannemuehler, M.J., Michalek, S.M., Lack of oral tolerance in C3H/HeJ mice. J. Exp. Med. 155 (1982), 605–610.
86. Kjer-Nielsen, L., Patel, O., Corbett, A.J., Le Nours, J., Meehan, B., Liu, L., Bhati, M., Chen, Z., Kostenko, L., Reantragoon, R., et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491 (2012), 717–723.
87. Klatt, N.R., Funderburg, N.T., Brenchley, J.M., Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 21 (2013), 6–13.
88. Laborel-Préneron, E., Bianchi, P., Boralevi, F., Lehours, P., Fraysse, F., Morice-Picard, F., Sugai, M., Sato'o, Y., Badiou, C., Lina, G., et al. Effects of the Staphylococcus aureus and Staphylococcus epidermidis Secretomes Isolated from the Skin Microbiota of Atopic Children on CD4+ T Cell Activation. PLoS ONE, 10, 2015, e0141067.
89. Lathrop, S.K., Bloom, S.M., Rao, S.M., Nutsch, K., Lio, C.W., Santacruz, N., Peterson, D.A., Stappenbeck, T.S., Hsieh, C.S., Peripheral education of the immune system by colonic commensal microbiota. Nature 478 (2011), 250–254.
90. Lee, Y.K., Menezes, J.S., Umesaki, Y., Mazmanian, S.K., Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 108:Suppl 1 (2011), 4615–4622.
91. Lewis, K.L., Caton, M.L., Bogunovic, M., Greter, M., Grajkowska, L.T., Ng, D., Klinakis, A., Charo, I.F., Jung, S., Gommerman, J.L., et al. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35 (2011), 780–791.
92. Ley, R.E., Peterson, D.A., Gordon, J.I., Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124 (2006), 837–848.
93. Li, Y., Innocentin, S., Withers, D.R., Roberts, N.A., Gallagher, A.R., Grigorieva, E.F., Wilhelm, C., Veldhoen, M., Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147 (2011), 629–640.
94. Li, F., Hao, X., Chen, Y., Bai, L., Gao, X., Lian, Z., Wei, H., Sun, R., Tian, Z., The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner. Nat. Commun., 7, 2017, 13839.
95. Loschko, J., Schreiber, H.A., Rieke, G.J., Esterházy, D., Meredith, M.M., Pedicord, V.A., Yao, K.H., Caballero, S., Pamer, E.G., Mucida, D., Nussenzweig, M.C., Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. J. Exp. Med. 213 (2016), 517–534.
96. Macia, L., Tan, J., Vieira, A.T., Leach, K., Stanley, D., Luong, S., Maruya, M., Ian McKenzie, C., Hijikata, A., Wong, C., et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun., 6, 2015, 6734.
97. Macpherson, A.J., Uhr, T., Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303 (2004), 1662–1665.
98. Martin, F.P., Dumas, M.E., Wang, Y., Legido-Quigley, C., Yap, I.K., Tang, H., Zirah, S., Murphy, G.M., Cloarec, O., Lindon, J.C., et al. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Mol. Syst. Biol., 3, 2007, 112.
99. Martinoli, C., Chiavelli, A., Rescigno, M., Entry route of Salmonella typhimurium directs the type of induced immune response. Immunity 27 (2007), 975–984.
100. Maslowski, K.M., Vieira, A.T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H.C., Rolph, M.S., Mackay, F., Artis, D., et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461 (2009), 1282–1286.
101. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O., Kasper, D.L., An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122 (2005), 107–118.
102. Mazmanian, S.K., Round, J.L., Kasper, D.L., A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453 (2008), 620–625.
103. McGuckin, M.A., Lindén, S.K., Sutton, P., Florin, T.H., Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 9 (2011), 265–278.
104. Medema, M.H., Fischbach, M.A., Computational approaches to natural product discovery. Nat. Chem. Biol. 11 (2015), 639–648.
105. Mortha, A., Chudnovskiy, A., Hashimoto, D., Bogunovic, M., Spencer, S.P., Belkaid, Y., Merad, M., Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science, 343, 2014, 1249288.
106. Mucida, D., Kutchukhidze, N., Erazo, A., Russo, M., Lafaille, J.J., Curotto de Lafaille, M.A., Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115 (2005), 1923–1933.
107. Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., Cheroutre, H., Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317 (2007), 256–260.
108. Mukherjee, S., Partch, C.L., Lehotzky, R.E., Whitham, C.V., Chu, H., Bevins, C.L., Gardner, K.H., Hooper, L.V., Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment. J. Biol. Chem. 284 (2009), 4881–4888.
109. Murray, B.E., Vancomycin-resistant enterococcal infections. N. Engl. J. Med. 342 (2000), 710–721.
110. Naik, S., Bouladoux, N., Wilhelm, C., Molloy, M.J., Salcedo, R., Kastenmuller, W., Deming, C., Quinones, M., Koo, L., Conlan, S., et al. Compartmentalized control of skin immunity by resident commensals. Science 337 (2012), 1115–1119.
111. Naik, S., Bouladoux, N., Linehan, J.L., Han, S.J., Harrison, O.J., Wilhelm, C., Conlan, S., Himmelfarb, S., Byrd, A.L., Deming, C., et al. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520 (2015), 104–108.
112. Narushima, S., Sugiura, Y., Oshima, K., Atarashi, K., Hattori, M., Suematsu, M., Honda, K., Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut Microbes 5 (2014), 333–339.
113. Niess, J.H., Adler, G., Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions. J. Immunol. 184 (2010), 2026–2037.
114. Niess, J.H., Brand, S., Gu, X., Landsman, L., Jung, S., McCormick, B.A., Vyas, J.M., Boes, M., Ploegh, H.L., Fox, J.G., et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307 (2005), 254–258.
115. O'Mahony, C., Scully, P., O'Mahony, D., Murphy, S., O'Brien, F., Lyons, A., Sherlock, G., MacSharry, J., Kiely, B., Shanahan, F., O'Mahony, L., Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog., 4, 2008, e1000112.
116. Ochoa-Repáraz, J., Mielcarz, D.W., Ditrio, L.E., Burroughs, A.R., Begum-Haque, S., Dasgupta, S., Kasper, D.L., Kasper, L.H., Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J. Immunol. 185 (2010), 4101–4108.
117. Oh, J.Z., Ravindran, R., Chassaing, B., Carvalho, F.A., Maddur, M.S., Bower, M., Hakimpour, P., Gill, K.P., Nakaya, H.I., Yarovinsky, F., et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41 (2014), 478–492.
118. + T cells. Science 349 (2015), 989–993.
119. Olszak, T., An, D., Zeissig, S., Vera, M.P., Richter, J., Franke, A., Glickman, J.N., Siebert, R., Baron, R.M., Kasper, D.L., Blumberg, R.S., Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336 (2012), 489–493.
120. Paget, C., Chow, M.T., Gherardin, N.A., Beavis, P.A., Uldrich, A.P., Duret, H., Hassane, M., Souza-Fonseca-Guimaraes, F., Mogilenko, D.A., Staumont-Sallé, D., et al. CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells. Immunol. Cell Biol. 93 (2015), 198–212.
121. Pamer, E.G., Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science 352 (2016), 535–538.
122. Panea, C., Farkas, A.M., Goto, Y., Abdollahi-Roodsaz, S., Lee, C., Koscsó, B., Gowda, K., Hohl, T.M., Bogunovic, M., Ivanov, I.I., Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses. Cell Rep. 12 (2015), 1314–1324.
123. Paulos, C.M., Wrzesinski, C., Kaiser, A., Hinrichs, C.S., Chieppa, M., Cassard, L., Palmer, D.C., Boni, A., Muranski, P., Yu, Z., et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117 (2007), 2197–2204.
124. Pearce, E.L., Walsh, M.C., Cejas, P.J., Harms, G.M., Shen, H., Wang, L.S., Jones, R.G., Choi, Y., Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460 (2009), 103–107.
125. Persson, E.K., Uronen-Hansson, H., Semmrich, M., Rivollier, A., Hägerbrand, K., Marsal, J., Gudjonsson, S., Håkansson, U., Reizis, B., Kotarsky, K., Agace, W.W., IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 38 (2013), 958–969.
126. Peterson, D.A., McNulty, N.P., Guruge, J.L., Gordon, J.I., IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2 (2007), 328–339.
127. Puel, A., Döffinger, R., Natividad, A., Chrabieh, M., Barcenas-Morales, G., Picard, C., Cobat, A., Ouachée-Chardin, M., Toulon, A., Bustamante, J., et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207 (2010), 291–297.
128. Qiu, J., Heller, J.J., Guo, X., Chen, Z.M., Fish, K., Fu, Y.X., Zhou, L., The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36 (2012), 92–104.
129. Qiu, J., Guo, X., Chen, Z.M., He, L., Sonnenberg, G.F., Artis, D., Fu, Y.X., Zhou, L., Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39 (2013), 386–399.
130. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., Medzhitov, R., Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118 (2004), 229–241.
131. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J.P., Ricciardi-Castagnoli, P., Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2 (2001), 361–367.
132. Rooks, M.G., Garrett, W.S., Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16 (2016), 341–352.
133. Round, J.L., Lee, S.M., Li, J., Tran, G., Jabri, B., Chatila, T.A., Mazmanian, S.K., The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332 (2011), 974–977.
134. Sanchez Rodriguez, R., Pauli, M.L., Neuhaus, I.M., Yu, S.S., Arron, S.T., Harris, H.W., Yang, S.H., Anthony, B.A., Sverdrup, F.M., Krow-Lucal, E., et al. Memory regulatory T cells reside in human skin. J. Clin. Invest. 124 (2014), 1027–1036.
135. Sano, T., Huang, W., Hall, J.A., Yang, Y., Chen, A., Gavzy, S.J., Lee, J.Y., Ziel, J.W., Miraldi, E.R., Domingos, A.I., et al. An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses. Cell 163 (2015), 381–393.
136. Satoh-Takayama, N., Vosshenrich, C.A., Lesjean-Pottier, S., Sawa, S., Lochner, M., Rattis, F., Mention, J.J., Thiam, K., Cerf-Bensussan, N., Mandelboim, O., et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29 (2008), 958–970.
137. Scharschmidt, T.C., Vasquez, K.S., Truong, H.A., Gearty, S.V., Pauli, M.L., Nosbaum, A., Gratz, I.K., Otto, M., Moon, J.J., Liese, J., et al. A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes. Immunity 43 (2015), 1011–1021.
138. Schiering, C., Krausgruber, T., Chomka, A., Fröhlich, A., Adelmann, K., Wohlfert, E.A., Pott, J., Griseri, T., Bollrath, J., Hegazy, A.N., et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513 (2014), 564–568.
139. Schlitzer, A., McGovern, N., Teo, P., Zelante, T., Atarashi, K., Low, D., Ho, A.W., See, P., Shin, A., Wasan, P.S., et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38 (2013), 970–983.
140. Sczesnak, A., Segata, N., Qin, X., Gevers, D., Petrosino, J.F., Huttenhower, C., Littman, D.R., Ivanov, I.I., The genome of th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment. Cell Host Microbe 10 (2011), 260–272.
141. Seekatz, A.M., Panda, A., Rasko, D.A., Toapanta, F.R., Eloe-Fadrosh, E.A., Khan, A.Q., Liu, Z., Shipley, S.T., Detolla, L.J., Sztein, M.B., Fraser, C.M., Differential response of the cynomolgus macaque gut microbiota to Shigella infection. PLoS ONE, 8, 2013, e64212.
142. + regulatory T cells. Science 349 (2015), 993–997.
143. Shaw, M.H., Kamada, N., Kim, Y.G., Núñez, G., Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J. Exp. Med. 209 (2012), 251–258.
144. Shen, Y., Giardino Torchia, M.L., Lawson, G.W., Karp, C.L., Ashwell, J.D., Mazmanian, S.K., Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12 (2012), 509–520.
145. Shi, C., Pamer, E.G., Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11 (2011), 762–774.
146. Shi, C., Jia, T., Mendez-Ferrer, S., Hohl, T.M., Serbina, N.V., Lipuma, L., Leiner, I., Li, M.O., Frenette, P.S., Pamer, E.G., Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Immunity 34 (2011), 590–601.
147. Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P.D., Manicassamy, S., Munn, D.H., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40 (2014), 128–139.
148. Sivan, A., Corrales, L., Hubert, N., Williams, J.B., Aquino-Michaels, K., Earley, Z.M., Benyamin, F.W., Lei, Y.M., Jabri, B., Alegre, M.L., et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350 (2015), 1084–1089.
149. Skabytska, Y., Wölbing, F., Günther, C., Köberle, M., Kaesler, S., Chen, K.M., Guenova, E., Demircioglu, D., Kempf, W.E., Volz, T., et al. Cutaneous innate immune sensing of Toll-like receptor 2-6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity 41 (2014), 762–775.
150. Smeekens, S.P., Huttenhower, C., Riza, A., van de Veerdonk, F.L., Zeeuwen, P.L., Schalkwijk, J., van der Meer, J.W., Xavier, R.J., Netea, M.G., Gevers, D., Skin microbiome imbalance in patients with STAT1/STAT3 defects impairs innate host defense responses. J. Innate Immun. 6 (2014), 253–262.
151. Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly-Y, M., Glickman, J.N., Garrett, W.S., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341 (2013), 569–573.
152. Sonnenberg, G.F., Monticelli, L.A., Alenghat, T., Fung, T.C., Hutnick, N.A., Kunisawa, J., Shibata, N., Grunberg, S., Sinha, R., Zahm, A.M., et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336 (2012), 1321–1325.
153. Stockinger, B., Di Meglio, P., Gialitakis, M., Duarte, J.H., The aryl hydrocarbon receptor: multitasking in the immune system. Annu. Rev. Immunol. 32 (2014), 403–432.
154. Sudo, N., Sawamura, S., Tanaka, K., Aiba, Y., Kubo, C., Koga, Y., The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J. Immunol. 159 (1997), 1739–1745.
155. Suffia, I.J., Reckling, S.K., Piccirillo, C.A., Goldszmid, R.S., Belkaid, Y., Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J. Exp. Med. 203 (2006), 777–788.
156. Sumaria, N., Roediger, B., Ng, L.G., Qin, J., Pinto, R., Cavanagh, L.L., Shklovskaya, E., Fazekas de St Groth, B., Triccas, J.A., Weninger, W., Cutaneous immunosurveillance by self-renewing dermal gammadelta T cells. J. Exp. Med. 208 (2011), 505–518.
157. Sun, C.M., Hall, J.A., Blank, R.B., Bouladoux, N., Oukka, M., Mora, J.R., Belkaid, Y., Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204 (2007), 1775–1785.
158. Sutherland, D.B., Suzuki, K., Fagarasan, S., Fostering of advanced mutualism with gut microbiota by Immunoglobulin A. Immunol. Rev. 270 (2016), 20–31.
159. Suzuki, K., Maruya, M., Kawamoto, S., Sitnik, K., Kitamura, H., Agace, W.W., Fagarasan, S., The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut. Immunity 33 (2010), 71–83.
160. Tada, T., Yamamura, S., Kuwano, Y., Abo, T., Level of myelopoiesis in the bone marrow is influenced by intestinal flora. Cell. Immunol. 173 (1996), 155–161.
161. Tait Wojno, E.D., Artis, D., Emerging concepts and future challenges in innate lymphoid cell biology. J. Exp. Med. 213 (2016), 2229–2248.
162. Talham, G.L., Jiang, H.Q., Bos, N.A., Cebra, J.J., Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infect. Immun. 67 (1999), 1992–2000.
163. Tan, T.G., Sefik, E., Geva-Zatorsky, N., Kua, L., Naskar, D., Teng, F., Pasman, L., Ortiz-Lopez, A., Jupp, R., Wu, H.J., et al. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proc. Natl. Acad. Sci. USA 113 (2016), E8141–E8150.
164. Thaiss, C.A., Zmora, N., Levy, M., Elinav, E., The microbiome and innate immunity. Nature 535 (2016), 65–74.
165. Trama, A.M., Moody, M.A., Alam, S.M., Jaeger, F.H., Lockwood, B., Parks, R., Lloyd, K.E., Stolarchuk, C., Scearce, R., Foulger, A., et al. HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria. Cell Host Microbe 16 (2014), 215–226.
166. Treiner, E., Duban, L., Bahram, S., Radosavljevic, M., Wanner, V., Tilloy, F., Affaticati, P., Gilfillan, S., Lantz, O., Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422 (2003), 164–169.
167. Trompette, A., Gollwitzer, E.S., Yadava, K., Sichelstiel, A.K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L.P., Harris, N.L., Marsland, B.J., Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20 (2014), 159–166.
168. Uematsu, S., Jang, M.H., Chevrier, N., Guo, Z., Kumagai, Y., Yamamoto, M., Kato, H., Sougawa, N., Matsui, H., Kuwata, H., et al. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat. Immunol. 7 (2006), 868–874.
169. Uematsu, S., Fujimoto, K., Jang, M.H., Yang, B.G., Jung, Y.J., Nishiyama, M., Sato, S., Tsujimura, T., Yamamoto, M., Yokota, Y., et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 9 (2008), 769–776.
170. Umesaki, Y., Setoyama, H., Matsumoto, S., Imaoka, A., Itoh, K., Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect. Immun. 67 (1999), 3504–3511.
171. Vaishnava, S., Yamamoto, M., Severson, K.M., Ruhn, K.A., Yu, X., Koren, O., Ley, R., Wakeland, E.K., Hooper, L.V., The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334 (2011), 255–258.
172. Valdez, Y., Brown, E.M., Finlay, B.B., Influence of the microbiota on vaccine effectiveness. Trends Immunol. 35 (2014), 526–537.
173. van der Windt, G.J., O'Sullivan, D., Everts, B., Huang, S.C., Buck, M.D., Curtis, J.D., Chang, C.H., Smith, A.M., Ai, T., Faubert, B., et al. CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability. Proc. Natl. Acad. Sci. USA 110 (2013), 14336–14341.
174. van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E.G., de Vos, W.M., Visser, C.E., Kuijper, E.J., Bartelsman, J.F., Tijssen, J.G., et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368 (2013), 407–415.
175. Veldhoen, M., Hirota, K., Westendorf, A.M., Buer, J., Dumoutier, L., Renauld, J.C., Stockinger, B., The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453 (2008), 106–109.
176. Vétizou, M., Pitt, J.M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M.P., Duong, C.P., et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350 (2015), 1079–1084.
177. Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D.P., Pfirschke, C., Engblom, C., Pittet, M.J., et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342 (2013), 971–976.
178. Volz, T., Skabytska, Y., Guenova, E., Chen, K.M., Frick, J.S., Kirschning, C.J., Kaesler, S., Röcken, M., Biedermann, T., Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells. J. Invest. Dermatol. 134 (2014), 96–104.
179. von Moltke, J., Ji, M., Liang, H.E., Locksley, R.M., Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529 (2016), 221–225.
180. Vonarbourg, C., Mortha, A., Bui, V.L., Hernandez, P.P., Kiss, E.A., Hoyler, T., Flach, M., Bengsch, B., Thimme, R., Hölscher, C., et al. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes. Immunity 33 (2010), 736–751.
181. Wade, T.K., Wade, W.F., Variable gene family usage of protective and non-protective anti-Vibrio cholerae O1 LPS antibody heavy chains. Microbiol. Immunol. 52 (2008), 611–620.
182. Wang, X., Cho, B., Suzuki, K., Xu, Y., Green, J.A., An, J., Cyster, J.G., Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers. J. Exp. Med. 208 (2011), 2497–2510.
183. Wannemuehler, M.J., Kiyono, H., Babb, J.L., Michalek, S.M., McGhee, J.R., Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germfree mice to sensitivity to oral tolerance induction. J. Immunol. 129 (1982), 959–965.
184. Weaver, C.T., Elson, C.O., Fouser, L.A., Kolls, J.K., The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu. Rev. Pathol. 8 (2013), 477–512.
185. Wei, M., Shinkura, R., Doi, Y., Maruya, M., Fagarasan, S., Honjo, T., 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 (2011), 264–270.
186. Weiner, H.L., da Cunha, A.P., Quintana, F., Wu, H., Oral tolerance. Immunol. Rev. 241 (2011), 241–259.
187. 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., Microbial colonization influences early B-lineage development in the gut lamina propria. Nature 501 (2013), 112–115.
188. Wohlfert, E.A., Grainger, J.R., Bouladoux, N., Konkel, J.E., Oldenhove, G., Ribeiro, C.H., Hall, J.A., Yagi, R., Naik, S., Bhairavabhotla, R., et al. GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. J Clin Invest, 2011.
189. Worbs, T., Bode, U., Yan, S., Hoffmann, M.W., Hintzen, G., Bernhardt, G., Förster, R., Pabst, O., Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J. Exp. Med. 203 (2006), 519–527.
190. Wu, H.J., Ivanov, I.I., Darce, J., Hattori, K., Shima, T., Umesaki, Y., Littman, D.R., Benoist, C., Mathis, D., Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32 (2010), 815–827.
191. Yang, Y., Torchinsky, M.B., Gobert, M., Xiong, H., Xu, M., Linehan, J.L., Alonzo, F., Ng, C., Chen, A., Lin, X., et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510 (2014), 152–156.
192. Yang, B.H., Hagemann, S., Mamareli, P., Lauer, U., Hoffmann, U., Beckstette, M., Föhse, L., Prinz, I., Pezoldt, J., Suerbaum, S., et al. Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol. 9 (2016), 444–457.
193. Yockey, L.J., Demehri, S., Turkoz, M., Turkoz, A., Ahern, P.P., Jassim, O., Manivasagam, S., Kearney, J.F., Gordon, J.I., Kopan, R., The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation. J. Invest. Dermatol. 133 (2013), 2714–2721.
194. Zelante, T., Iannitti, R.G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D'Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39 (2013), 372–385.
195. Zeng, M.Y., Cisalpino, D., Varadarajan, S., Hellman, J., Warren, H.S., Cascalho, M., Inohara, N., Núñez, G., Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens. Immunity 44 (2016), 647–658.
196. Zhang, D., Chen, G., Manwani, D., Mortha, A., Xu, C., Faith, J.J., Burk, R.D., Kunisaki, Y., Jang, J.E., Scheiermann, C., et al. Neutrophil ageing is regulated by the microbiome. Nature 525 (2015), 528–532.