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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/15913
Title: Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice
Authors: Natividad, Jane M.; Huang, Xianxi; Slack, Emma; Jury, Jennifer; Sanz, Yolanda; David, Chella; Denou, Emmanuel; Yang, Pinchang; Murray, Joseph; McCoy, Kathy D.; Verdu, Elena F.
Issue Date: 31-Jul-2009
Publisher: Public Library of Science
Citation: PLoS ONE 4(7): e6472 (2009)
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.
Description: 11 pages, 8 figures.
Publisher version (URL): http://dx.doi.org/10.1371/journal.pone.0006472
URI: http://hdl.handle.net/10261/15913
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0006472
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