Interactions between commensal intestinal bacteria and the immune system

Abstract

Although we might shudder at the thought of billions of bacteria living in our lower intestine, we are colonized by these passengers shortly after birth. However, the relationship is mostly of mutual benefit, and they shape our immune system throughout life. Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity and their relevance to the effects of hygiene on human disease.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Keeping germ-free mice in an isolator.
Figure 2: The presence of intestinal bacteria has a large impact on lymphoid structures of both the intestine and systemic tissues.
Figure 3: Immune defences against commensal intestinal bacteria.

References

  1. 1

    Clark, R. W. The Life and Work of J. B. S. Haldane (Oxford Univ. Press, 1984).

    Google Scholar 

  2. 2

    Sartor, R. B. Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am. J. Gastroenterol. 92, 5S–11S (1997).

    CAS  PubMed  Google Scholar 

  3. 3

    Macpherson, A. J., Hunziker, L., McCoy, K. & Lamarre, A. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect. 3, 1021–1035 (2001).

    CAS  PubMed  Article  Google Scholar 

  4. 4

    Macpherson, A. J., Martinic, M. M. & Harris, N. The functions of mucosal T cells in containing the indigenous flora of the intestine. Cell. Mol. Life Sci. 59, 2088–2096 (2002).

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Bauer, H., Horowitz, R. E., Levenson, S. M. & Popper, H. The response of lymphatic tissue to the microbial flora. Studies on germfree mice. Am. J. Pathol. 42, 471–479 (1963).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Manolios, N., Geczy, C. L. & Schrieber, L. High endothelial venule morphology and function are inducible in germ-free mice: a possible role for interferon-γ. Cell. Immunol. 117, 136–151 (1988).

    CAS  PubMed  Article  Google Scholar 

  7. 7

    Benveniste, J., Lespinats, G., Adam, C. & Salomon, J. C. Immunoglobulins in intact, immunized, and contaminated axenic mice: study of serum IgA. J. Immunol. 107, 1647–1655 (1971).

    CAS  PubMed  Google Scholar 

  8. 8

    Hooper, L. V. et al. Molecular analysis of commensal host–microbial relationships in the intestine. Science 291, 881–884 (2001).

    CAS  Article  PubMed  Google Scholar 

  9. 9

    Mackie, R., Sghir, A. & Gaskins, H. R. Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 69, 1035S–1045S (1999).

    CAS  PubMed  Article  Google Scholar 

  10. 10

    Ganz, T. Defensins: antimicrobial peptides of innate immunity. Nature Rev. Immunol. 3, 710–720 (2003).

    CAS  Article  Google Scholar 

  11. 11

    Berg, R. D. The indigenous gastrointestinal microflora. Trends Microbiol. 4, 430–435 (1996).

    CAS  PubMed  Article  Google Scholar 

  12. 12

    Wells, C. L., Maddaus, M. A. & Simmons, R. L. Proposed mechanisms for the translocation of intestinal bacteria. Rev. Infect. Dis. 10, 958–979 (1988).

    CAS  PubMed  Article  Google Scholar 

  13. 13

    O'Boyle, C. J. et al. Microbiology of bacterial translocation in humans. Gut 42, 29–35 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14

    Macpherson, A. J. & Uhr, T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662–1665 (2004).

    CAS  Article  PubMed  Google Scholar 

  15. 15

    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  Article  PubMed  Google Scholar 

  16. 16

    Shiloh, M. U. et al. Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity 10, 29–38 (1999).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17

    Crabbe, P. A., Nash, D. R., Bazin, H., Eyssen, H. & Heremans, J. F. Immunohistochemical observations on lymphoid tissues from conventional and germ-free mice. Lab. Invest. 22, 448–457 (1970).

    CAS  PubMed  Google Scholar 

  18. 18

    Benveniste, J., Lespinats, G. & Salomon, J. Serum and secretory IgA in axenic and holoxenic mice. J. Immunol. 107, 1656–1662 (1971).

    CAS  PubMed  Google Scholar 

  19. 19

    Hooijkaas, H., Benner, R., Pleasants, J. R. & Wostmann, B. S. Isotypes and specificities of immunoglobulins produced by germ-free mice fed chemically defined ultrafiltered 'antigen-free' diet. Eur. J. Immunol. 14, 1127–1130 (1984).

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Wostmann, B. S., Pleasants, J. R. & Bealmear, P. Dietary stimulation of immune mechanisms. Fed. Proc. 30, 1779–1784 (1971).

    CAS  PubMed  Google Scholar 

  21. 21

    Wostmann, B. S. & Pleasants, J. R. The germ-free animal fed chemically defined diet: a unique tool. Proc. Soc. Exp. Biol. Med. 198, 539–546 (1991).

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Garside, P. & Mowat, A. M. Oral tolerance. Semin. Immunol. 13, 177–185 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23

    Bos, N. A. & Ploplis, V. A. Humoral immune response to 2,4-dinitrophenyl–keyhole limpet hemocyanin in antigen-free, germ-free and conventional BALB/c mice. Eur. J. Immunol. 24, 59–65 (1994).

    CAS  PubMed  Article  Google Scholar 

  24. 24

    Williams, G. T., Jolly, C. J., Kohler, J. & Neuberger, M. S. The contribution of somatic hypermutation to the diversity of serum immunoglobulin: dramatic increase with age. Immunity 13, 409–417 (2000).

    CAS  PubMed  Article  Google Scholar 

  25. 25

    Bakker, R., Lasonder, E. & Bos, N. A. Measurement of affinity in serum samples of antigen-free, germ-free and conventional mice after hyperimmunization with 2,4-dinitrophenyl–keyhole limpet hemocyanin, using surface plasmon resonance. Eur. J. Immunol. 25, 1680–1686 (1995).

    CAS  PubMed  Article  Google Scholar 

  26. 26

    Moxon, E. R. & Anderson, P. Meningitis caused by Haemophilus influenzae in infant rats: protective immunity and antibody priming by gastrointestinal colonization with Escherichia coli. J. Infect. Dis. 140, 471–478 (1979).

    CAS  PubMed  Article  Google Scholar 

  27. 27

    Probst, H. C., Lagnel, J., Kollias, G. & van den Broek, M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18, 713–720 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28

    Sudo, N. et al. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J. Immunol. 159, 1739–1745 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259–1260 (1989).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30

    Matricardi, P. M. et al. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ 314, 999–1003 (1997).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31

    Matricardi, P. M. et al. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. BMJ 320, 412–417 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32

    Shirakawa, T., Enomoto, T., Shimazu, S. & Hopkin, J. M. The inverse association between tuberculin responses and atopic disorder. Science 275, 77–79 (1997).

    CAS  Article  PubMed  Google Scholar 

  33. 33

    Kilpelainen, M., Terho, E. O., Helenius, H. & Koskenvuo, M. Farm environment in childhood prevents the development of allergies. Clin. Exp. Allergy 30, 201–108 (2000).

    CAS  PubMed  Article  Google Scholar 

  34. 34

    Riedler, J., Eder, W., Oberfeld, G. & Schreuer, M. Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin. Exp. Allergy 30, 194–200 (2000).

    CAS  PubMed  Article  Google Scholar 

  35. 35

    Riedler, J. et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129–1133 (2001).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Von Ehrenstein, O. S. et al. Reduced risk of hay fever and asthma among children of farmers. Clin. Exp. Allergy 30, 187–193 (2000).

    CAS  PubMed  Article  Google Scholar 

  37. 37

    McIntire, J. J. et al. Hepatitis A virus link to atopic disease. Nature 425, 576 (2003).

    CAS  Article  PubMed  Google Scholar 

  38. 38

    McIntire, J. J. et al. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nature Immunol. 2, 1109–1116 (2001).

    CAS  Article  Google Scholar 

  39. 39

    Busse, W. W. & Lemanske, R. F. Asthma. N. Engl. J. Med. 344, 350–362 (2001).

    CAS  Article  PubMed  Google Scholar 

  40. 40

    Scrivener, S. et al. Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 358, 1493–1499 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41

    Lammas, D. A., Casanova, J. L. & Kumararatne, D. S. Clinical consequences of defects in the IL-12-dependent interferon-γ (IFN-γ) pathway. Clin. Exp. Immunol. 121, 417–425 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42

    Stene, l. C. & Nafstad, P. Relation between occurrence of type 1 diabetes and asthma. Lancet 357, 607–608 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43

    Kero, J., Gissler, M., Hemminki, E. & Isolauri, E. Could TH1 and TH2 diseases coexist? Evaluation of asthma incidence in children with coeliac disease, type 1 diabetes, or rheumatoid arthritis: a register study. J. Allergy Clin. Immunol. 108, 781–783 (2001).

    CAS  PubMed  Article  Google Scholar 

  44. 44

    McGuirk, P., McCann, C. & Mills, K. H. G. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J. Exp. Med. 195, 221–231 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45

    MacDonald, A. J. et al. CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J. Infect. Dis. 185, 720–727 (2002).

    CAS  PubMed  Article  Google Scholar 

  46. 46

    Kullberg, M. C. et al. Bacteria-triggered CD4+ T regulatory cells suppress Helicobacter hepaticus-induced colitis. J. Exp. Med. 196, 505–515 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47

    Doetze, A. et al. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by TH3/TR1-type cytokines IL-10 and transforming growth factor-β but not by a TH1 to TH2 shift. Int. Immunol. 12, 623–630 (2000).

    CAS  Article  PubMed  Google Scholar 

  48. 48

    Hori, S., Takahashi, T. & Sakaguchi, S. Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv. Immunol. 81, 331–371 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49

    Shih, F. F., Mandik-Nayak, L., Wipke, B. T. & Allen, P. M. Massive thymic deletion results in systemic autoimmunity through elimination of CD4+CD25+ T regulatory cells. J. Exp. Med. 199, 323–335 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50

    Hori, S., Nomura, M. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003).

    CAS  Article  PubMed  Google Scholar 

  51. 51

    Gambineri, E., Torgerson, T. R. & Ochs, H. D. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr. Opin. Rheumatol. 15, 430–435 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52

    Jordan, M. S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nature Immunol. 2, 301–306 (2001).

    CAS  Article  Google Scholar 

  53. 53

    Dewhirst, F. E. et al. Phylogeny of the defined murine microbiota: altered Schaedler flora. Appl. Environ. Microbiol. 65, 3287–3292 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    East, J., Prosser, P. R., Holborow, E. J. & Jaquet, H. Autoimmune reactions and virus-like particles in germ-free NZB mice. Lancet 1, 755–757 (1967).

    CAS  Article  PubMed  Google Scholar 

  55. 55

    Unni, K. K., Holley, K. E., McDuffie, F. C. & Titus, J. L. Comparative study of NZB mice under germ-free and conventional conditions. J. Rheumatol. 2, 36–44 (1975).

    CAS  PubMed  Google Scholar 

  56. 56

    Goverman, J. et al. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72, 551–560 (1993).

    CAS  PubMed  Article  Google Scholar 

  57. 57

    Murakami, M. et al. Effects of breeding environments on generation and activation of autoreactive B1 cells in anti-red blood cell autoantibody transgenic mice. J. Exp. Med. 185, 791–794 (1997).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58

    Penhale, W. J. & Young, P. R. The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroiditis. Clin. Exp. Immunol. 72, 288–292. (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Maldonado, M. A. et al. The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. J. Immunol. 162, 6322–6330 (1999).

    CAS  PubMed  Google Scholar 

  60. 60

    Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263–274 (1993).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Sadlack, B. et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75, 253–261 (1993).

    CAS  Article  PubMed  Google Scholar 

  62. 62

    Mombaerts, P. et al. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75, 274–282 (1993).

    CAS  Article  PubMed  Google Scholar 

  63. 63

    Simpson, S. J., de Jong, Y. P., Comiskey, M. & Terhorst, C. T cells in mouse models of gut inflammation. Chem. Immunol. 71, 118–138 (1998).

    CAS  PubMed  Article  Google Scholar 

  64. 64

    Murakami, K. et al. Germ-free condition and the susceptibility of BALB/c mice to post-thymectomy autoimmune gastritis. Autoimmunity 12, 69–70 (1992).

    CAS  PubMed  Article  Google Scholar 

  65. 65

    Suzuki, T. et al. in Immune Deficient Animals in Biomedical Research (eds Rygaard, J., Graem, N. & Sprang-Thomsen, M.) 112–116 (Karger, Basel, 1987).

    Google Scholar 

  66. 66

    Leiter, E. in The Role of Microorganisms in Non-infectious Disease (eds de Vries, R. R. P., Cohen, I. R. & van Rood, J. J.) 39–55 (Springer, Berlin, 1990).

    Google Scholar 

  67. 67

    Hunziker, L. et al. Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections. Nature Immunol. 4, 343–349 (2003).

    CAS  Article  Google Scholar 

  68. 68

    Chu, H. W., Honour, J. M., Rawlinson, C. A., Harbeck, R. J. & Martin, R. J. Effects of respiratory Mycoplasma pnemoniae infection on allergen-induced bronchial hyperresponsiveness and lung inflammation in mice. Infect. Immun. 71, 1520–1526 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69

    Erb, K. J., Holloway, J. W., Sobeck, A., Moll, H. & Le Gros, G. L. Infection of mice with Mycobacterium bovis-Bacillus Calmette-Guerin (BCG) suppresses allergen-induced airway eosinophilia. J. Exp. Med. 187, 561–569 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70

    Marsland, B. J. et al. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells. Proc. Natl Acad. Sci. USA 101, 6116–6121 (2004).

    CAS  PubMed  Article  Google Scholar 

  71. 71

    Bachmann, M. F. et al. The role of antibody concentration and avidity in antiviral protection. Science 276, 2024–2027 (1997).

    CAS  PubMed  Article  Google Scholar 

  72. 72

    Freer, G. et al. Vesicular stomatitis virus Indiana glycoprotein as a T cell-dependent and -independent antigen. J. Virol. 68, 3650–3655 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Sangster, M. Y. et al. An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T–B interactions. J. Exp. Med. 198, 1011–1021 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. 74

    Oxenius, A., Zinkernagel, R. M. & Hengartner, H. Comparison of activation versus induction of unresponsiveness of virus-specific CD4+ and CD8+ T cells upon acute versus persistent viral infection. Immunity 9, 449–457 (1998).

    CAS  PubMed  Article  Google Scholar 

  75. 75

    Hunziker, L., Klenerman, P., Zinkernagel, R. M. & Ehl, S. Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells. Eur. J. Immunol. 32, 374–382 (2002).

    CAS  PubMed  Article  Google Scholar 

  76. 76

    Klein, L. et al. Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor. Eur. J. Immunol. 33, 806–814 (2003).

    CAS  PubMed  Article  Google Scholar 

  77. 77

    Moskophidis, D., Lechner, F., Pircher, H. & Zinkernagel, R. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 362, 758–761 (1993).

    CAS  Article  PubMed  Google Scholar 

  78. 78

    Probst, H. C., Dumrese, T. & van den Broek, M. Competition for APC by CTLs of different specificities is not functionally important during induction of antiviral responses. J. Immunol. 168, 5387–5391 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79

    Kalliomäki, M. et al. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J. Allergy Clin. Immunol. 107, 129–134 (2001).

    PubMed  Article  Google Scholar 

  80. 80

    Heeger, P. S. et al. Revisiting tolerance induced by autoantigen in incomplete Freund's adjuvant. J. Immunol. 164, 5771–5781 (2000).

    CAS  PubMed  Article  Google Scholar 

  81. 81

    Weisburg, W. G., Barns, S. M., Pelletier, D. A. & Lane, D. J. 16S ribosomal DNA amplification for phylogenetic study. J. Bacteriol. 173, 697–703 (1991).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82

    Schaedler, R. W., Dubos, R. & Costello, R. Association of germfree mice with bacteria isolated from normal mice. J. Exp. Med. 122, 77–83 (1965).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. 83

    Orcutt, R. P., Gianni, F. J. & Judge, R. J. Development of an 'Altered Schaedler flora' for NCI gnotobiotic rodents. Microecol. Ther. 17, 59 (1987).

    Google Scholar 

  84. 84

    Wills-Karp, M., Santeliz, J. & Karp, C. L. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev. Immunol. 1, 69–75 (2001).

    CAS  Article  Google Scholar 

  85. 85

    Matricardi, P. M. & Ronchetti, R. Are infections protecting from atopy? Curr. Opin. Allergy Clin. Immunol. 1, 413–419 (2001).

    CAS  PubMed  Article  Google Scholar 

  86. 86

    Maggi, E. et al. Reciprocal regulator effects of IFN-γ and IL-4 on the in vitro development of human TH1 and TH2 clones. J. Immunol. 148, 2142–2147 (1992).

    CAS  PubMed  Google Scholar 

  87. 87

    Snapper, C. M. & Paul, W. E. Interferon-γ and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236, 944–947 (1987).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. 88

    Prescott, S. L. et al. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the TH2 cytokine profile. J. Immunol. 160, 4730–4737 (1998).

    CAS  PubMed  Google Scholar 

  89. 89

    Holt, P. G., Rowe, J., Loh, R. & Sly, P. D. Developmental factors associated with risk for atopic disease: implications for vaccine strategies in early childhood. Vaccine 21, 3432–3445 (2003).

    CAS  PubMed  Article  Google Scholar 

  90. 90

    Zuany-Amorim, Z. et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T cells. Nature Med. 8, 625–629 (2002).

    CAS  PubMed  Article  Google Scholar 

  91. 91

    Bashir, M. E. H., Anderson, P., Fuss, I. J., Shi, H. N. & Nagler-Anderson, C. An enteric helminth infection protects against an allergic response to dietary antigen. J. Immunol. 169, 3284–3292 (2002).

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Andrew J. Macpherson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Gene

CD4

CD8

CD25

CD45

Fas

FOXP3

IL-10

interferon-γ

TIM1

transforming growth factor-β1

Glossary

DEFENSINS

A family of proteins exhibiting bactericidal properties. They are secreted by immune cells (particularly neutrophils), intestinal Paneth cells and epithelial cells.

EXHAUSTION

Non-responsiveness of the immune system resulting from the deletion of specific thymocytes (central tolerance) and the deletion or functional inactivation of specific T cells in the periphery (peripheral tolerance) in the presence of large quantities of antigen.

IGNORANCE

Non-responsiveness of the immune system in the presence of a given antigen, despite the existence of specific T and B cells capable of mounting a functional response.

INFLAMMATORY BOWEL DISEASE

Immune-mediated inflammation of the bowel. There are two main forms: Crohn's disease, which is a granulomatous segmental inflammation affecting any part of the intestine, and ulcerative colitis, which is a mucosal inflammation involving the rectum and extending for a variable distance along the colon. In developed countries, the incidence of inflammatory bowel disease is approximately 1 in 50,000. It usually starts in early adult life and continues afterwards with a relapsing, remitting course.

LAMINA PROPRIA

The layer of the intestine between the epithelial cells and the most superficial smooth-muscle layer.

MIMICRY

Resemblance between epitopes contained within microbial and host proteins, leading to crossreactivity of T cells in the host.

MUTUALISM

The relationship between two different species that live in close proximity and benefit from one another.

PEYER'S PATCHES

Collections of lymphoid tissue located in the mucosa of the small intestine, with an outer epithelial layer containing specialized epithelial cells, called M cells.

REPERTOIRE

The spectrum of B or T cells. Defined according to the specificities of the B-cell- or T-cell-receptors that are present immediately before onset of a clinically important infection.

T-CELL-DEPENDENT ANTIGEN

To generate an antibody response to a T-cell-dependent protein antigen requires recognition of the antigen (in the context of MHC molecules) by helper T cells and cooperation between those antigen-specific T cells and B cells that recognize the same antigen.

TOLL-LIKE RECEPTORS

Cell-associated pattern-recognition receptors that recognize molecules unique to microorganisms, resulting in immune-cell activation and production of pro-inflammatory molecules.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Macpherson, A., Harris, N. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478–485 (2004). https://doi.org/10.1038/nri1373

Download citation

Further reading