Host responses to intestinal microbial antigens in gluten-sensitive mice

Natividad, Jane M; Huang, Xianxi; Slack, Emma; Jury, Jennifer; Sanz, Yolanda; David, Chella; Denou, Emmanuel; Yang, Pinchang; Murray, Joseph; McCoy, Kathy D; Verdú, Elena F (2009). Host responses to intestinal microbial antigens in gluten-sensitive mice. PLoS ONE, 4(7), e6472. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0006472

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BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. CONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
UniBE Contributor:	Slack, Emma
ISSN:	1932-6203
Publisher:	Public Library of Science
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:11
Last Modified:	05 Dec 2022 14:21
Publisher DOI:	10.1371/journal.pone.0006472
PubMed ID:	19649259
Web of Science ID:	000268637600019
URI:	https://boris.unibe.ch/id/eprint/31226 (FactScience: 195647)