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PMID: 22923434 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.

Science (New York, N.Y.) ·Vol. 337 ·No. 6101 ·2012-09-21 ·Pages 1553-6

Hand TW, Dos Santos LM, Bouladoux N, Molloy MJ, Pagán AJ, Pepper M, Maynard CL, Elson CO, Belkaid Y

Abstract

The mammalian gastrointestinal tract contains a large and diverse population of commensal bacteria and is also one of the primary sites of exposure to pathogens. How the immune system perceives commensals in the context of mucosal infection is unclear. Here, we show that during a gastrointestinal infection, tolerance to commensals is lost, and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are phenotypically and functionally consistent with pathogen-specific T cells. Our results suggest that during a gastrointestinal infection, the immune response to commensals parallels the immune response against pathogenic microbes and that adaptive responses against commensals are an integral component of mucosal immunity.

MeSH Terms
Acute Disease Animals Bacteria/immunology Bacterial Translocation CD4-Positive T-Lymphocytes/immunology Flagellin/immunology Gastrointestinal Tract/immunology,microbiology,parasitology Immunity, Mucosal Immunologic Memory Intestinal Diseases, Parasitic/immunology,parasitology Intestinal Mucosa/microbiology,parasitology Lymphocyte Activation Metagenome/immunology Mice Mice, Inbred C57BL Mice, Transgenic Th1 Cells/immunology Time Factors Toxoplasma/immunology,physiology Toxoplasmosis, Animal/immunology,parasitology
Chemicals
Flagellin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Hand Timothy W
Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Dos Santos Liliane M
Bouladoux Nicolas
Molloy Michael J
Pagán Antonio J
Pepper Marion
Maynard Craig L
Elson Charles O
Belkaid Yasmine
References (31)
31 references, click to expand
  1. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection.
    Immunity. 2009 Nov 20;31(5):772-86 PMID: 19896394
  2. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota.
    Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19256-61 PMID: 19889972
  3. A human gut microbial gene catalogue established by metagenomic sequencing.
    Nature. 2010 Mar 4;464(7285):59-65 PMID: 20203603
  4. Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells.
    J Immunol. 2011 Feb 1;186(3):1531-7 PMID: 21178008
  5. Toll-like receptor control of the adaptive immune responses.
    Nat Immunol. 2004 Oct;5(10):987-95 PMID: 15454922
  6. Immunology of Toxoplasma gondii.
    Immunol Rev. 2011 Mar;240(1):269-85 PMID: 21349099
  7. Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii.
    J Immunol. 2006 Dec 15;177(12):8785-95 PMID: 17142781
  8. Bacterial flagellin is a dominant antigen in Crohn disease.
    J Clin Invest. 2004 May;113(9):1296-306 PMID: 15124021
  9. Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology.
    Pediatr Infect Dis J. 2006 Jan;25(1):2-7 PMID: 16395094
  10. Human nutrition, the gut microbiome and the immune system.
    Nature. 2011 Jun 15;474(7351):327-36 PMID: 21677749
  11. Isolation of flagellated bacteria implicated in Crohn's disease.
    Inflamm Bowel Dis. 2007 Oct;13(10):1191-201 PMID: 17712838
  12. Memory CD4 T cells emerge from effector T-cell progenitors.
    Nature. 2008 Mar 20;452(7185):356-60 PMID: 18322463
  13. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    Nat Genet. 2010 Dec;42(12):1118-25 PMID: 21102463
  14. Induction of intestinal Th17 cells by segmented filamentous bacteria.
    Cell. 2009 Oct 30;139(3):485-98 PMID: 19836068
  15. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000.
    Bull World Health Organ. 2003;81(3):197-204 PMID: 12764516
  16. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses.
    Immunity. 2009 Oct 16;31(4):677-89 PMID: 19833089
  17. The mucosal firewalls against commensal intestinal microbes.
    Semin Immunopathol. 2009 Jul;31(2):145-9 PMID: 19707762
  18. Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection.
    Gut. 2011 Nov;60(11):1506-19 PMID: 21515549
  19. Intestinal bacterial colonization induces mutualistic regulatory T cell responses.
    Immunity. 2011 May 27;34(5):794-806 PMID: 21596591
  20. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria.
    Science. 2004 Mar 12;303(5664):1662-5 PMID: 15016999
  21. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude.
    Immunity. 2007 Aug;27(2):203-13 PMID: 17707129
  22. Gut commensal bacteria direct a protective immune response against Toxoplasma gondii.
    Cell Host Microbe. 2009 Aug 20;6(2):187-96 PMID: 19683684
  23. Peripheral education of the immune system by colonic commensal microbiota.
    Nature. 2011 Sep 21;478(7368):250-4 PMID: 21937990
  24. Differential expression of Ly6C and T-bet distinguish effector and memory Th1 CD4(+) cell properties during viral infection.
    Immunity. 2011 Oct 28;35(4):633-46 PMID: 22018471
  25. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism.
    Science. 2009 Jul 31;325(5940):617-20 PMID: 19644121
  26. Heterogeneity of CD4+ memory T cells: functional modules for tailored immunity.
    Eur J Immunol. 2009 Aug;39(8):2076-82 PMID: 19672903
  27. Induction of colonic regulatory T cells by indigenous Clostridium species.
    Science. 2011 Jan 21;331(6015):337-41 PMID: 21205640
  28. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine.
    Cell. 2010 Jun 25;141(7):1135-45 PMID: 20602997
  29. Inflammatory bowel disease.
    Annu Rev Immunol. 2010;28:573-621 PMID: 20192811
  30. Naive and memory CD4+ T cell survival controlled by clonal abundance.
    Science. 2006 Apr 7;312(5770):114-6 PMID: 16513943
  31. Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells.
    Nat Immunol. 2010 Jan;11(1):83-9 PMID: 19935657
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2012-09-21
Epub
2012-00-23
Pages
1553-6
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3784339
Subset
IM
Grants
NIAID NIH HHS · T32 AI007051 · United States
Intramural NIH HHS · Z99 AI999999 · United States
NIDDK NIH HHS · R24 DK064400 · United States
NIDDK NIH HHS · P01 DK071176 · United States
NIDDK NIH HHS · DK64400 · United States
NIDDK NIH HHS · DK071176 · United States
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