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TRIF Signaling Drives Homeostatic Intestinal Epithelial Antimicrobial Peptide Expression
- Stockinger, S. (author)
- Duerr, C. U. (author)
- Fulde, M. (author)
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- Dolowschiak, T. (author)
- Pott, J. (author)
- Yang, I. (author)
- Eibach, D. (author)
- Akira, S. (author)
- Suerbaum, S. (author)
- Brugman, M. (author)
- Hornef, M. W. (author)
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- (creator_code:org_t)
- 2014-10-15
- 2014
- English.
- In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:8, s. 4223-4234
- Journal article (peer-reviewed)
Abstract
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- Recent results indicate a significant contribution of innate immune signaling to maintain mucosal homeostasis, but the precise underlying signal transduction pathways are ill-defined. By comparative analysis of intestinal epithelial cells isolated from conventionally raised and germ-free mice, as well as animals deficient in the adaptor molecules MyD88 and TRIF, the TLR3 and TLR4, as well as the type I and III IFN receptors, we demonstrate significant TLR-mediated signaling under homeostatic conditions. Surprisingly, homeostatic expression of Reg3 gamma and Paneth cell enteric antimicrobial peptides critically relied on TRIF and, in part, TLR3 but was independent of IFN receptor signaling. Reduced antimicrobial peptide expression was associated with significantly lower numbers of Paneth cells and a reduced Paneth cell maturation and differentiation factor expression in TRIF mutant compared with wild-type epithelium. This phenotype was not transferred to TRIF-sufficient germ-free animals during cohousing. Low antimicrobial peptide expression in TRIF-deficient mice caused reduced immediate killing of orally administered bacteria but was not associated with significant alterations in the overall composition of the enteric microbiota. The phenotype was rapidly restored in a TRIF-independent fashion after transient epithelial damage. Our results identify TRIF signaling as a truly homeostatic pathway to maintain intestinal epithelial barrier function revealing fundamental differences in the innate immune signaling between mucosal homeostasis and tissue repair.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- DOUBLE-STRANDED-RNA
- TOLL-LIKE RECEPTORS
- PANETH CELLS
- INNATE IMMUNITY
- BACTERICIDAL LECTIN
- ALPHA-DEFENSINS
- HOST-DEFENSE
- IKK-BETA
- IN-VIVO
- INFLAMMATION
- Immunology
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- ref (subject category)
- art (subject category)
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- Stockinger, S.
- Duerr, C. U.
- Fulde, M.
- Dolowschiak, T.
- Pott, J.
- Yang, I.
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- Eibach, D.
- Bäckhed, Fredrik ...
- Akira, S.
- Suerbaum, S.
- Brugman, M.
- Hornef, M. W.
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- MEDICAL AND HEALTH SCIENCES
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- University of Gothenburg
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