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PMID: 20566828 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 185 ·No. 2 ·2010-07-15 ·Pages 1177-85

Van Maele L, Carnoy C, Cayet D, Songhet P, Dumoutier L, Ferrero I, Janot L, Erard F, Bertout J, Leger H, Sebbane F, Benecke A, Renauld JC, Hardt WD, Ryffel B, Sirard JC

Abstract

In adaptive immunity, Th17 lymphocytes produce the IL-17 and IL-22 cytokines that stimulate mucosal antimicrobial defenses and tissue repair. In this study, we observed that the TLR5 agonist flagellin induced swift and transient transcription of genes encoding IL-17 and IL-22 in lymphoid, gut, and lung tissues. This innate response also temporarily enhanced the expression of genes associated with the antimicrobial Th17 signature. The source of the Th17-related cytokines was identified as novel populations of CD3(neg)CD127(+) immune cells among which CD4-expressing cells resembling lymphoid tissue inducer cells. We also demonstrated that dendritic cells are essential for expression of Th17-related cytokines and so for stimulation of innate cells. These data define that TLR-induced activation of CD3(neg)CD127(+) cells and production of Th17-related cytokines may be crucial for the early defenses against pathogen invasion of host tissues.

MeSH Terms
Animals CD3 Complex/genetics,immunology,metabolism Cells, Cultured Dendritic Cells/drug effects,immunology,metabolism Female Flagellin/pharmacology Flow Cytometry Gene Expression/drug effects,immunology Ileum/drug effects,immunology,metabolism Interleukin-17/genetics,immunology,metabolism Interleukin-7 Receptor alpha Subunit/genetics,immunology,metabolism Interleukins/genetics,immunology,metabolism Lymphoid Tissue/cytology,immunology,metabolism Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, SCID Mice, Transgenic Mucous Membrane/cytology,immunology,metabolism Oligonucleotide Array Sequence Analysis Signal Transduction/immunology Spleen/cytology,immunology,metabolism Toll-Like Receptor 5/genetics,immunology,metabolism
Chemicals
CD3 Complex Interleukin-17 Interleukin-7 Receptor alpha Subunit Interleukins Toll-Like Receptor 5 Flagellin interleukin-22
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Van Maele Laurye
Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, France.
Carnoy Christophe
Cayet Delphine
Songhet Pascal
Dumoutier Laure
Ferrero Isabel
Janot Laure
Erard François
Bertout Julie
Leger Hélène
Sebbane Florent
Benecke Arndt
Renauld Jean-Christophe
Hardt Wolf-Dietrich
Ryffel Bernhard
Sirard Jean-Claude
References (51)
51 references, click to expand
  1. In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain.
    J Biol Chem. 2004 Oct 8;279(41):42984-92 PMID: 15302888
  2. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells.
    Nat Immunol. 2006 Aug;7(8):868-74 PMID: 16829963
  3. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation.
    J Immunol. 2008 Jun 15;180(12):8280-5 PMID: 18523294
  4. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.
    Nat Med. 2008 Mar;14(3):275-81 PMID: 18264110
  5. Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin.
    Eur J Immunol. 2009 Jun;39(6):1587-96 PMID: 19424969
  6. Structure and signalling in the IL-17 receptor family.
    Nat Rev Immunol. 2009 Aug;9(8):556-67 PMID: 19575028
  7. Both radioresistant and hemopoietic cells promote innate and adaptive immune responses to flagellin.
    J Immunol. 2008 Jun 1;180(11):7184-92 PMID: 18490717
  8. Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa.
    Trends Microbiol. 2004 Nov;12(11):509-17 PMID: 15488392
  9. Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent step in DeltainvG S. Typhimurium colitis.
    J Exp Med. 2008 Feb 18;205(2):437-50 PMID: 18268033
  10. Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia.
    J Exp Med. 2007 May 14;204(5):995-1001 PMID: 17470641
  11. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells.
    Nat Immunol. 2009 Jan;10(1):66-74 PMID: 19029905
  12. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis.
    J Exp Med. 2009 Feb 16;206(2):299-311 PMID: 19204111
  13. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease.
    Immunity. 2008 Dec 19;29(6):947-57 PMID: 19100701
  14. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5.
    Nat Immunol. 2008 Jul;9(7):769-76 PMID: 18516037
  15. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens.
    Nat Med. 2008 Mar;14(3):282-9 PMID: 18264109
  16. War and peace at mucosal surfaces.
    Nat Rev Immunol. 2004 Dec;4(12):953-64 PMID: 15573130
  17. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
    J Exp Med. 2009 Jul 6;206(7):1465-72 PMID: 19564350
  18. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses.
    Immunity. 2009 Jan 16;30(1):108-19 PMID: 19144317
  19. Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor.
    Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10144-9 PMID: 10954742
  20. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis.
    Nature. 2008 Nov 27;456(7221):507-10 PMID: 18987631
  21. Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells.
    J Immunol. 2005 Aug 1;175(3):1551-7 PMID: 16034093
  22. Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells.
    J Immunol. 2009 Aug 15;183(4):2217-21 PMID: 19635901
  23. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells.
    Immunity. 2007 May;26(5):643-54 PMID: 17521585
  24. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection.
    J Exp Med. 2008 Feb 18;205(2):323-9 PMID: 18227219
  25. Normalization using weighted negative second order exponential error functions (NeONORM) provides robustness against asymmetries in comparative transcriptome profiles and avoids false calls.
    Genomics Proteomics Bioinformatics. 2006 May;4(2):90-109 PMID: 16970549
  26. Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin.
    Nat Immunol. 2009 Jan;10(1):75-82 PMID: 19029904
  27. Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells.
    J Exp Med. 2007 Oct 29;204(11):2579-90 PMID: 17923506
  28. CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles.
    Mucosal Immunol. 2009 Nov;2(6):486-94 PMID: 19741597
  29. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut.
    Immunity. 2008 Aug 15;29(2):261-71 PMID: 18656387
  30. IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors.
    J Exp Med. 2010 Feb 15;207(2):273-80 PMID: 20142427
  31. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large.
    Annu Rev Immunol. 2006;24:353-89 PMID: 16551253
  32. Hyporesponsiveness of intestinal dendritic cells to TLR stimulation is limited to TLR4.
    J Immunol. 2009 Feb 15;182(4):2405-15 PMID: 19201895
  33. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production.
    Blood. 2004 Sep 15;104(6):1778-83 PMID: 15166032
  34. EBER2 RNA-induced transcriptome changes identify cellular processes likely targeted during Epstein Barr Virus infection.
    BMC Res Notes. 2008 Oct 28;1:100 PMID: 18957101
  35. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells.
    J Exp Med. 2009 Jan 16;206(1):43-9 PMID: 19114668
  36. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models.
    Science. 2008 Apr 11;320(5873):226-30 PMID: 18403709
  37. The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development.
    Nat Immunol. 2009 Oct;10(10):1118-24 PMID: 19749763
  38. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22.
    J Exp Med. 2009 Jan 16;206(1):35-41 PMID: 19114665
  39. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model.
    J Exp Med. 2007 Nov 26;204(12):2803-12 PMID: 18025126
  40. The AP-1 transcription factor Batf controls T(H)17 differentiation.
    Nature. 2009 Jul 16;460(7253):405-9 PMID: 19578362
  41. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.
    Nature. 2009 Feb 5;457(7230):722-5 PMID: 18978771
  42. IL-17 and Th17 Cells.
    Annu Rev Immunol. 2009;27:485-517 PMID: 19132915
  43. Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13722-7 PMID: 11717433
  44. Cytokine-mediated regulation of antimicrobial proteins.
    Nat Rev Immunol. 2008 Nov;8(11):829-35 PMID: 18949018
  45. Immune response to Salmonella: location, location, location?
    Immunity. 2002 Mar;16(3):325-8 PMID: 11911817
  46. Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production.
    J Immunol. 2007 Apr 1;178(7):4466-72 PMID: 17372004
  47. Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection.
    J Infect Dis. 2010 Feb 15;201(4):534-43 PMID: 20064069
  48. Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response.
    J Immunol. 2004 Jun 1;172(11):6922-30 PMID: 15153511
  49. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense.
    Immunity. 2008 Dec 19;29(6):958-70 PMID: 19084435
  50. Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells.
    J Immunol. 2009 May 15;182(10):5904-8 PMID: 19414740
  51. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells.
    Nat Immunol. 2009 Jan;10(1):83-91 PMID: 19029903
Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1000115
Published
2010-07-15
Epub
2010-00-21
Pages
1177-85
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3060348
Subset
IM
External Links
PubMed source DOI: 10.4049/jimmunol.1000115 PMC Full Text View journal details
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