Compartmentalized and systemic control of tissue immunity by commensals

Abstract

The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective, we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology.

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Figure 1: Tissue-specific modes of host-commensal interactions at distinct barrier sites.
Figure 2: Localized and systemic regulation of the immune system by distinct commensal niches.

References

  1. 1

    Shklovskaya, E. et al. Langerhans cells are precommitted to immune tolerance induction. Proc. Natl. Acad. Sci. USA 108, 18049–18054 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Chu, C.C. et al. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J. Exp. Med. 209, 935–945 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Igyarto, B.Z. et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35, 260–272 (2011).

    CAS  PubMed  Google Scholar 

  4. 4

    Scott, C.L., Aumeunier, A.M. & Mowat, A.M. Intestinal CD103+ dendritic cells: master regulators of tolerance? Trends Immunol. 32, 412–419 (2011).

    CAS  PubMed  Google Scholar 

  5. 5

    Spits, H. & Cupedo, T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu. Rev. Immunol. 30, 647–675 (2012).

    CAS  PubMed  Google Scholar 

  6. 6

    Owens, B.M. & Simmons, A. Intestinal stromal cells in mucosal immunity and homeostasis. Mucosal Immunol. 6, 224–234 (2013).

    CAS  PubMed  Google Scholar 

  7. 7

    Malhotra, D., Fletcher, A.L. & Turley, S.J. Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity. Immunol. Rev. 251, 160–176 (2013).

    PubMed  PubMed Central  Google Scholar 

  8. 8

    Matzinger, P. & Kamala, T. Tissue-based class control: the other side of tolerance. Nat. Rev. Immunol. 11, 221–230 (2011).

    CAS  PubMed  Google Scholar 

  9. 9

    Hooper, L.V. & Macpherson, A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159–169 (2010).

    CAS  PubMed  Google Scholar 

  10. 10

    Molloy, M.J., Bouladoux, N. & Belkaid, Y. Intestinal microbiota: shaping local and systemic immune responses. Semin. Immunol. 24, 58–66 (2012).

    CAS  PubMed  Google Scholar 

  11. 11

    Blumberg, R. & Powrie, F. Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med. 4, 137rv137 (2012).

    Google Scholar 

  12. 12

    Smith, M.I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Foulongne, V. et al. Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PLoS ONE 7, e38499 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Iliev, I.D. et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336, 1314–1317 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Eckburg, P.B., Lepp, P.W. & Relman, D.A. Archaea and their potential role in human disease. Infect. Immun. 71, 591–596 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Grice, E.A. & Segre, J.A. The human microbiome: our second genome. Annu. Rev. Genomics Hum. Genet. 13, 151–170 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Ley, R.E., Peterson, D.A. & Gordon, J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006).

    CAS  PubMed  Google Scholar 

  19. 19

    Medini, D. et al. Microbiology in the post-genomic era. Nat. Rev. Microbiol. 6, 419–430 (2008).

    CAS  PubMed  Google Scholar 

  20. 20

    Kuczynski, J. et al. Experimental and analytical tools for studying the human microbiome. Nat. Rev. Genet. 13, 47–58 (2012).

    CAS  Google Scholar 

  21. 21

    Costello, E.K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Eckburg, P.B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    PubMed  PubMed Central  Google Scholar 

  23. 23

    Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Tilg, H. & Kaser, A. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest. 121, 2126–2132 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Tlaskalova-Hogenova, H. et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol. Immunol. 8, 110–120 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Pride, D.T. et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 6, 915–926 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Human Microbiome Project Consortium. A framework for human microbiome research. Nature 486, 215–221 (2012).

  29. 29

    Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  30. 30

    Grice, E.A. & Segre, J.A. The skin microbiome. Nat. Rev. Microbiol. 9, 244–253 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Grice, E.A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 1190–1192 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Segata, N. et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 13, R42 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Beck, J.M., Young, V.B. & Huffnagle, G.B. The microbiome of the lung. Transl. Res. 160, 258–266 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Charlson, E.S. et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J. Respir. Crit. Care Med. 184, 957–963 (2011).

    PubMed  PubMed Central  Google Scholar 

  35. 35

    Abubucker, S. et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol. 8, e1002358 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Cantarel, B.L., Lombard, V. & Henrissat, B. Complex carbohydrate utilization by the healthy human microbiome. PLoS ONE 7, e28742 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA 108, 5354–5359 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Abt, M.C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158–170 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Ochoa-Reparaz, J. et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J. Immunol. 185, 4101–4108 (2010).

    CAS  PubMed  Google Scholar 

  40. 40

    Wu, H.J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538–541 (2011).

    CAS  PubMed  Google Scholar 

  42. 42

    Wen, L. et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 1109–1113 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Kriegel, M.A. et al. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc. Natl. Acad. Sci. USA 108, 11548–11553 (2011).

    CAS  PubMed  Google Scholar 

  44. 44

    Hill, D.A. et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat. Med. 18, 538–546 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Clarke, T.B. et al. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16, 228–231 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Shi, C. et al. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Immunity 34, 590–601 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Maslowski, K.M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Kong, H.H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Abreu, N.A. et al. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci. Transl. Med. 4, 151ra124 (2012).

    PubMed  PubMed Central  Google Scholar 

  50. 50

    Hilty, M. et al. Disordered microbial communities in asthmatic airways. PLoS ONE 5, e8578 (2010).

    PubMed  PubMed Central  Google Scholar 

  51. 51

    Belda-Ferre, P. et al. The oral metagenome in health and disease. ISME J. 6, 46–56 (2012).

    CAS  PubMed  Google Scholar 

  52. 52

    Srinivasan, S. et al. Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis. PLoS ONE 5, e10197 (2010).

    PubMed  PubMed Central  Google Scholar 

  53. 53

    Crispe, I.N. The liver as a lymphoid organ. Annu. Rev. Immunol. 27, 147–163 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Corbitt, N. et al. Gut bacteria drive Kupffer cell expansion via MAMP-mediated ICAM-1 induction on sinusoidal endothelium and influence preservation-reperfusion injury after orthotopic liver transplantation. Am. J. Pathol. 182, 180–191 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Bigorgne, A.E. & Crispe, I.N. TLRs in hepatic cellular crosstalk. Gastroenterol. Res. Pract. 2010, 618260 (2010).

    PubMed  PubMed Central  Google Scholar 

  56. 56

    Lunz, J.G. III, Specht, S.M., Murase, N., Isse, K. & Demetris, A.J. Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity. Hepatology 46, 1946–1959 (2007).

    CAS  PubMed  Google Scholar 

  57. 57

    Wilson, N.S. et al. Normal proportion and expression of maturation markers in migratory dendritic cells in the absence of germs or Toll-like receptor signaling. Immunol. Cell Biol. 86, 200–205 (2008).

    CAS  PubMed  Google Scholar 

  58. 58

    Walton, K.L., He, J., Kelsall, B.L., Sartor, R.B. & Fisher, N.C. Dendritic cells in germ-free and specific pathogen-free mice have similar phenotypes and in vitro antigen presenting function. Immunol. Lett. 102, 16–24 (2006).

    CAS  PubMed  Google Scholar 

  59. 59

    Hill, D.A. et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 3, 148–158 (2009).

    PubMed  PubMed Central  Google Scholar 

  60. 60

    Grice, E.A. et al. A diversity profile of the human skin microbiota. Genome Res. 18, 1043–1050 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Christoph, T. et al. The human hair follicle immune system: cellular composition and immune privilege. Br. J. Dermatol. 142, 862–873 (2000).

    CAS  PubMed  Google Scholar 

  62. 62

    Nagao, K. et al. Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat. Immunol. 13, 744–752 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Iwase, T. et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010).

    CAS  PubMed  Google Scholar 

  64. 64

    Gallo, R.L. & Hooper, L.V. Epithelial antimicrobial defence of the skin and intestine. Nat. Rev. Immunol. 12, 503–516 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Cash, H.L., Whitham, C.V., Behrendt, C.L. & Hooper, L.V. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313, 1126–1130 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Lai, Y. et al. Commensal bacteria regulate Toll-like receptor 3–dependent inflammation after skin injury. Nat. Med. 15, 1377–1382 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Loots, M.A. et al. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J. Invest. Dermatol. 111, 850–857 (1998).

    CAS  PubMed  Google Scholar 

  69. 69

    Grice, E.A. et al. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proc. Natl. Acad. Sci. USA 107, 14799–14804 (2010).

    CAS  PubMed  Google Scholar 

  70. 70

    Ivanov, I.I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Gallo, R.L. & Nakatsuji, T. Microbial symbiosis with the innate immune defense system of the skin. J. Invest. Dermatol. 131, 1974–1980 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Kong, H.H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Gao, Z., Tseng, C.H., Strober, B.E., Pei, Z. & Blaser, M.J. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS ONE 3, e2719 (2008).

    PubMed  PubMed Central  Google Scholar 

  74. 74

    Sims, J.E. & Smith, D.E. The IL-1 family: regulators of immunity. Nat. Rev. Immunol. 10, 89–102 (2010).

    CAS  Google Scholar 

  75. 75

    Nestle, F.O., Kaplan, D.H. & Barker, J. Psoriasis. N. Engl. J. Med. 361, 496–509 (2009).

    CAS  PubMed  Google Scholar 

  76. 76

    Ortega, C. et al. IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete TH17-related cytokines. J. Leukoc. Biol. 86, 435–443 (2009).

    CAS  PubMed  Google Scholar 

  77. 77

    Eyerich, S. et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J. Clin. Invest. 119, 3573–3585 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Leonardi, C. et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N. Engl. J. Med. 366, 1190–1199 (2012).

    CAS  PubMed  Google Scholar 

  79. 79

    Papp, K.A. et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N. Engl. J. Med. 366, 1181–1189 (2012).

    CAS  PubMed  Google Scholar 

  80. 80

    Zheng, Y. et al. Interleukin-22, a TH17 cytokine, mediates IL-23–induced dermal inflammation and acanthosis. Nature 445, 648–651 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Lai, Y. et al. The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury. Immunity 37, 74–84 (2012).

    CAS  PubMed  Google Scholar 

  82. 82

    Avila, M., Ojcius, D.M. & Yilmaz, O. The oral microbiota: living with a permanent guest. DNA Cell Biol. 28, 405–411 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Yilmaz, O. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay. Microbiology 154, 2897–2903 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Dixon, D.R., Reife, R.A., Cebra, J.J. & Darveau, R.P. Commensal bacteria influence innate status within gingival tissues: a pilot study. J. Periodontol. 75, 1486–1492 (2004).

    PubMed  Google Scholar 

  85. 85

    Desvarieux, M. et al. Periodontal microbiota and carotid intima-media thickness: the oral infections and vascular disease epidemiology study (INVEST). Circulation 111, 576–582 (2005).

    PubMed  PubMed Central  Google Scholar 

  86. 86

    Hajishengallis, G. et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 10, 497–506 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Egan, C.E., Cohen, S.B. & Denkers, E.Y. Insights into inflammatory bowel disease using Toxoplasma gondii as an infectious trigger. Immunol. Cell Biol. 90, 668–675 (2012).

    CAS  Google Scholar 

  88. 88

    Heimesaat, M.M. et al. Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J. Immunol. 177, 8785–8795 (2006).

    CAS  Google Scholar 

  89. 89

    Lupp, C. et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2, 204 (2007).

    CAS  PubMed  Google Scholar 

  90. 90

    Stecher, B. et al. Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biol. 5, 2177–2189 (2007).

    CAS  PubMed  Google Scholar 

  91. 91

    Farage, M. & Maibach, H. Lifetime changes in the vulva and vagina. Arch. Gynecol. Obstet. 273, 195–202 (2006).

    PubMed  Google Scholar 

  92. 92

    Hickey, R.J., Zhou, X., Pierson, J.D., Ravel, J. & Forney, L.J. Understanding vaginal microbiome complexity from an ecological perspective. Transl. Res. 160, 267–282 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Antonio, M.A., Hawes, S.E. & Hillier, S.L. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J. Infect. Dis. 180, 1950–1956 (1999).

    CAS  PubMed  Google Scholar 

  94. 94

    Spurbeck, R.R. & Arvidson, C.G. Lactobacilli at the front line of defense against vaginally acquired infections. Future Microbiol. 6, 567–582 (2011).

    CAS  PubMed  Google Scholar 

  95. 95

    Rose, W.A. II et al. Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures. PLoS ONE 7, e32728 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Zhou, X. et al. Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. Microbiology 150, 2565–2573 (2004).

    CAS  PubMed  Google Scholar 

  97. 97

    Witkin, S.S., Alvi, S., Bongiovanni, A.M., Linhares, I.M. & Ledger, W.J. Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide. FEMS Immunol. Med. Microbiol. 61, 153–158 (2011).

    CAS  PubMed  Google Scholar 

  98. 98

    Genc, M.R. et al. Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth. Am. J. Obstet. Gynecol. 191, 1324–1330 (2004).

    CAS  PubMed  Google Scholar 

  99. 99

    Gabryszewski, S.J. et al. Lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection. J. Immunol. 186, 1151–1161 (2011).

    CAS  PubMed  Google Scholar 

  100. 100

    Garcia-Crespo, K.E. et al. Lactobacillus priming of the respiratory tract: heterologous immunity and protection against lethal pneumovirus infection. Antiviral Res. 97, 270–279 (2013).

    CAS  PubMed  Google Scholar 

  101. 101

    Herbst, T. et al. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir. Crit. Care Med. 184, 198–205 (2011).

    CAS  PubMed  Google Scholar 

  102. 102

    Hand, T.W. et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337, 1553–1556 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Haas, A. et al. Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection. Gut 60, 1506–1519 (2011).

    CAS  PubMed  Google Scholar 

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Acknowledgements

Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. We thank members of the Belkaid laboratory for helpful discussions, particularly S. Spencer and J. Grainger for critical reading of the manuscript.

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Correspondence to Yasmine Belkaid.

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Belkaid, Y., Naik, S. Compartmentalized and systemic control of tissue immunity by commensals. Nat Immunol 14, 646–653 (2013). https://doi.org/10.1038/ni.2604

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