Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The role of the immune system in governing host-microbe interactions in the intestine

An Erratum to this article was published on 21 January 2014

This article has been updated

Abstract

The mammalian intestinal tract harbors a diverse community of trillions of microorganisms, which have co-evolved with the host immune system for millions of years. Many of these microorganisms perform functions critical for host physiology, but the host must remain vigilant to control the microbial community so that the symbiotic nature of the relationship is maintained. To facilitate homeostasis, the immune system ensures that the diverse microbial load is tolerated and anatomically contained, while remaining responsive to microbial breaches and invasion. Although the microbiota is required for intestinal immune development, immune responses also regulate the structure and composition of the intestinal microbiota. Here we discuss recent advances in our understanding of these complex interactions and their implications for human health and disease.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Spatial distribution and composition of the microbiota along the intestinal tract.
Figure 2: Anatomical containment of the microbiota along the intestine.
Figure 3: Innate barriers ensure a tolerant response to the microbiota.

Similar content being viewed by others

Change history

  • 20 September 2013

    In the version of this article initially published, a label was missing from Figure 2. The lymphoid structure in the large intestine should be labeled 'Isolated lymphoid follicle'. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Xu, J. & Gordon, J.I. Honor thy symbionts. Proc. Natl. Acad. Sci. USA 100, 10452–10459 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Eckburg, P.B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).This is the first comprehensive study to use a culture-independent approach to describe the composition of the intestinal microbiota in healthy adult humans.

    PubMed  PubMed Central  Google Scholar 

  3. Ley, R.E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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

  5. Sekirov, I., Russel, S.L., Antunes, L.C.M. & Finlay, B.B. Gut microbiota in health and disease. Physiol. Rev. 90, 859–904 (2010).

    CAS  PubMed  Google Scholar 

  6. Garrett, W.S., Gordon, J.I. & Glimcher, L.H. Homeostasis and inflammation in the intestine. Cell 140, 859–870 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Willing, B.P., Russell, S.L. & Finlay, B.B. Shifting the balance: antibiotic effects on host-microbiota mutualism. Nat. Rev. Microbiol. 9, 233–243 (2011).

    CAS  PubMed  Google Scholar 

  8. Maslowski, K.M. & Mackay, C.R. Diet, gut microbiota and immune responses. Nat. Immunol. 12, 5–9 (2011).

    CAS  PubMed  Google Scholar 

  9. Gill, N., Wlodarska, M. & Finlay, B.B. Roadblocks in the gut: barriers to enteric infection. Cell. Microbiol. 13, 660–669 (2011).

    CAS  PubMed  Google Scholar 

  10. Willing, B.P., Gill, N. & Finlay, B.B. The role of the immune system in regulating the microbiota. Gut Microbes 1, 213–223 (2010).

    PubMed  PubMed Central  Google Scholar 

  11. 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 

  12. Kim, Y.S. & Ho, S.B. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr. Gastroenterol. Rep. 12, 319–330 (2010).

    PubMed  PubMed Central  Google Scholar 

  13. Johansson, M.E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl. Acad. Sci. USA 105, 15064–15069 (2008).This study provides the first visual evidence of the composition of the mucus layer, highlighting the function of the mucus layer in segregating the microbiota away from the host epithelium.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wlodarska, M. et al. Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium–induced colitis. Infect. Immun. 79, 1536–1545 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Fyderek, K. Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J. Gastroenterol. 15, 5287 (2009).

    PubMed  PubMed Central  Google Scholar 

  16. Johansson, M., Larsson, J. & Hansson, G. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc. Natl. Acad. Sci. USA 108 (suppl. 1), 4659–4665 (2011).

    CAS  PubMed  Google Scholar 

  17. Podolsky, D.K. et al. Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. J. Biol. Chem. 268, 6694–6702 (1993).

    CAS  PubMed  Google Scholar 

  18. Artis, D. et al. RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract. Proc. Natl. Acad. Sci. USA 101, 13596–13600 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bevins, C.L. & Salzman, N.H. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat. Rev. Microbiol. 9, 356–368 (2011).

    CAS  PubMed  Google Scholar 

  20. Vaishnava, S., Behrendt, C.L., Ismail, A.S., Eckmann, L. & Hooper, L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. USA 105, 20858–20863 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Vaishnava, S. et al. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Selsted, M.E. & Ouellette, A.J. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 6, 551–557 (2005).

    CAS  PubMed  Google Scholar 

  23. Salzman, N. et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 11, 76–83 (2010).

    CAS  PubMed  Google Scholar 

  24. 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, 1891–1900 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kaiser, V. & Diamond, G. Expression of mammalian defensin genes. J. Leukoc. Biol. 68, 779–784 (2000).

    CAS  PubMed  Google Scholar 

  26. Menendez, A. et al. Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell α-defensins. J. Innate Immun. 5, 39–49 (2013).

    CAS  PubMed  Google Scholar 

  27. Chu, H. et al. Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337, 477–481 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Schroeder, B. et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature 469, 419–423 (2011).

    CAS  PubMed  Google Scholar 

  29. Spits, H. & Di Santo, J.P. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat. Immunol. 12, 21–27 (2011).

    CAS  PubMed  Google Scholar 

  30. 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 

  31. Sonnenberg, G. & Artis, D. Innate lymphoid cell interactions with microbiota: implications for intestinal health and disease. Immunity 37, 601–610 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012).

    CAS  PubMed  Google Scholar 

  33. Sawa, S. et al. RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat. Immunol. 12, 320–326 (2011).

    CAS  PubMed  Google Scholar 

  34. Lochner, M. et al. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgamma t and LTi cells. J. Exp. Med. 208, 125–134 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Sonnenberg, G. et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336, 1321–1325 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Sonnenberg, G.F., Monticelli, L.A., Elloso, M.M., Fouser, L.A. & Artis, D. CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34, 122–134 (2011).

    CAS  PubMed  Google Scholar 

  37. Monticelli, L.A. et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 12, 1045–1054 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Powell, N. et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity 37, 674–684 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Cebra, J.J. Influences of microbiota on intestinal immune system development. Am. J. Clin. Nutr. 69, 1046S–1051S (1999).

    CAS  PubMed  Google Scholar 

  40. Abreu, M.T. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat. Rev. Immunol. 10, 131–144 (2010).

    CAS  PubMed  Google Scholar 

  41. Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805–820 (2010).

    CAS  PubMed  Google Scholar 

  42. Carvalho, F.A., Aitken, J.D., Vijay-Kumar, M. & Gewirtz, A.T. Toll-like receptor-gut microbiota interactions: perturb at your own risk!. Annu. Rev. Physiol. 74, 177–198 (2012).

    CAS  PubMed  Google Scholar 

  43. Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Exp. Med. 209, 1445–1456 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Vijay-Kumar, M. et al. Deletion of TLR5 results in spontaneous colitis in mice. J. Clin. Invest. 117, 3909–3921 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Slack, E. et al. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325, 617–620 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Salcedo, R. et al. MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J. Exp. Med. 207, 1625–1636 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745–757 (2011).This work demonstrates that both the microbiota and the host's genotype can affect mucosal disease, and disease susceptibility can be transferred to another wild-type host by a colitogenic microbiota.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Huber, S. et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491, 259–263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Santaolalla, R. & Abreu, M.T. Innate immunity in the small intestine. Curr. Opin. Gastroenterol. 28, 124–129 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Coombes, J.L. & Powrie, F. Dendritic cells in intestinal immune regulation. Nat. Rev. Immunol. 8, 435–446 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Farache, J. et al. Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. Immunity 38, 581–595 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. McDole, J.R. et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345–349 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Knoop, K.A., Miller, M.J. & Newberry, R.D. Transepithelial antigen delivery in the small intestine: different paths, different outcomes. Curr. Opin. Gastroenterol. 29, 112–118 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Mestecky, J. & Russell, M.W. Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces. Immunol. Lett. 124, 57–62 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Niess, J.H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254–258 (2005).

    CAS  PubMed  Google Scholar 

  57. Macpherson, A.J. & Uhr, T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662–1665 (2004).This report demonstrates that specialized bacteria-laden dendritic cells can induce protective IgA to protect the host epithelium from bacterial invasion, and migration of these dendritic cells is limited to the mesenteric lymph nodes of the mucosal immune system.

    CAS  PubMed  Google Scholar 

  58. Hapfelmeier, S. et al. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328, 1705–1709 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 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, 328–339 (2007).

    CAS  PubMed  Google Scholar 

  60. Macpherson, A.J. et al. A primitive T cell–independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288, 2222–2226 (2000).

    CAS  PubMed  Google Scholar 

  61. Suzuki, K. et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc. Natl. Acad. Sci. USA 101, 1981–1986 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Wei, M. et al. 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, 264–270 (2011).

    CAS  PubMed  Google Scholar 

  63. Slack, E., Balmer, M.L., Fritz, J.H. & Hapfelmeier, S. Functional flexibility of intestinal IgA—broadening the fine line. Front. Immunol. 3, 100 (2012).

    PubMed  PubMed Central  Google Scholar 

  64. Cong, Y., Feng, T., Fujihashi, K., Schoeb, T. & Elson, C. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc. Natl. Acad. Sci. USA 106, 19256–19261 (2009).This study extends the role for T reg cells to include the induction and maintainance of IgA+ plasma cells in the intestine, and promotion of mutualism with the microbiota.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Read, S., Malmstrom, V. & Powrie, F. Cytotoxic T lymphocyte–associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J. Exp. Med. 192, 295–302 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Maloy, K.J. et al. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197, 111–119 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Li, M.O., Wan, Y.Y. & Flavell, R.A. T cell-produced transforming growth factor-β1 controls T cell tolerance and regulates TH1- and TH17-cell differentiation. Immunity 26, 579–591 (2007).

    CAS  PubMed  Google Scholar 

  68. Ahern, P.P. et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity 33, 279–288 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Littman, D.R. & Rudensky, A.Y. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 140, 845–858 (2010).

    CAS  PubMed  Google Scholar 

  70. Chaudhry, A. et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986–991 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Maynard, C.L. et al. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3 precursor cells in the absence of interleukin 10. Nat. Immunol. 8, 931–941 (2007).

    CAS  PubMed  Google Scholar 

  72. Foussat, A. et al. A comparative study between T regulatory type 1 and CD4+CD25+ T cells in the control of inflammation. J. Immunol. 171, 5018–5026 (2003).

    CAS  PubMed  Google Scholar 

  73. Lupp, C. et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2, 119–129 (2007).This study reveals that the composition of the intestinal microbiota changes in distinctive ways in response to infection and inflammation, and underscores the importance of intestinal microbial ecosystems during infection.

    CAS  PubMed  Google Scholar 

  74. Littman, D.R. & Pamer, E.G. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe 10, 311–323 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 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 

  76. Winter, S.E. et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 467, 426–429 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Winter, S.E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Gill, N. et al. Neutrophil elastase alters the murine gut microbiota resulting in enhanced Salmonella colonization. PLoS ONE 7, e49646 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Stelter, C. et al. Salmonella-induced mucosal lectin RegIIIb kills competing gut microbiota. PLoS ONE 6, e20749 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Raetz, M. et al. Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-gamma–dependent elimination of Paneth cells. Nat. Immunol. 14, 136–142 (2013).

    CAS  PubMed  Google Scholar 

  81. Khor, B., Gardet, A. & Xavier, R.J. Genetics and pathogenesis of inflammatory bowel disease. Nature 474, 307–317 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53, 1658–1664 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibity to Crohn's disease. Nature 411, 603–606 (2001).

    CAS  PubMed  Google Scholar 

  85. Hugot, J.P. et al. Association of NOD-2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001)References 84 and 85 reported NOD2 as a susceptibility locus for Crohn's disease, providing evidence the first genetic link to IBD and insight into how a dysregulated immune response to the microbiota can lead to inflammatory diseases.

    CAS  PubMed  Google Scholar 

  86. Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl. Acad. Sci. USA 106, 15813–15818 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Kobayashi, K.S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–734 (2005).

    CAS  PubMed  Google Scholar 

  88. Wehkamp, J. et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc. Natl. Acad. Sci. USA 102, 18129–18134 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Simms, L.A. et al. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease. Gut 57, 903–910 (2008).

    CAS  PubMed  Google Scholar 

  90. Bernink, J.H. et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat. Immunol. 14, 221–229 (2013).

    CAS  PubMed  Google Scholar 

  91. Mehandru, S. et al. Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection. J. Virol. 81, 599–612 (2007).

    CAS  PubMed  Google Scholar 

  92. Brenchley, J.M. et al. Differential TH17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 112, 2826–2835 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Gosselin, A. et al. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J. Immunol. 184, 1604–1616 (2010).

    CAS  PubMed  Google Scholar 

  94. Brenchley, J.M. & Douek, D.C. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 1, 23–30 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Raffatellu, M. et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat. Med. 14, 421–428 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Macal, M. et al. Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses. Mucosal Immunol. 1, 475–488 (2008).

    CAS  PubMed  Google Scholar 

  97. Cecchinato, V. et al. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol. 1, 279–288 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Favre, D. et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 5, e1000295 (2009).

    PubMed  PubMed Central  Google Scholar 

  99. Saxena, D. et al. Human microbiome and HIV/AIDS. Curr. HIV/AIDS Rep. 9, 44–51 (2012).

    PubMed  PubMed Central  Google Scholar 

  100. Ellis, C.L. et al. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J. Acquir. Immune Defic. Syndr. 57, 363–370 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Malamut, G. et al. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease. Am. J. Gastroenterol. 105, 2262–2275 (2010).

    CAS  PubMed  Google Scholar 

  102. Shulzhenko, N. et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat. Med. 17, 1585–1593 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Mannon, P.J. et al. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology 131, 748–756 (2006).

    CAS  PubMed  Google Scholar 

  104. Scamurra, R.W. et al. Mucosal plasma cell repetoire during HIV-1 infection. J. Immunol. 169, 4008–4016 (2002).

    CAS  PubMed  Google Scholar 

  105. Man, S.M., Kaakoush, N.O. & Mitchell, H.M. The role of bacteria and pattern-recognition receptors in Crohn's disease. Nat. Rev. Gastroenterol. Hepatol. 8, 152–168 (2011).

    PubMed  Google Scholar 

  106. Duerkop, B.A. & Hooper, L.V. Resident viruses and their interactions with the immune system. Nat. Immunol. (18 Jun 2013) doi:10.1038/ni.2614.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank M. Wlodarska, L. Reynolds and N. Gill for the critical revision of this manuscript and thoughtful insights. The Finlay laboratory is supported by operating grants from Canadian Institutes of Health Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B Brett Finlay.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, E., Sadarangani, M. & Finlay, B. The role of the immune system in governing host-microbe interactions in the intestine. Nat Immunol 14, 660–667 (2013). https://doi.org/10.1038/ni.2611

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.2611

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing