Host responses to intestinal microbial antigens in gluten-sensitive mice

Jane M. Natividad, Xianxi Huang, Emma Slack, Jennifer Jury, Yolanda Sanz, Chella David, Emmanuel Denou, Pinchang Yang, Joseph Murray, Kathy D. McCoy, Elena F. Verdú

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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-γ 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-γ 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.

Original languageEnglish (US)
Article numbere6472
JournalPloS one
Volume4
Issue number7
DOIs
StatePublished - Jul 31 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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