| Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice (2009) | |||||||||||||
Abstract | |||||||||||||
| 11 pages, 8 figures.. [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.. This work was supported by a grant by the Canadian Association of Gastroenterology (CAG)/Canadian Institute of Health Research (CIHR) and by the Canadian Celiac Association New Investigator Award (E. Verdu). E. Verdu holds a McMaster University Dep. of Medicine Internal Career Research Award. Dr K. McCoy holds a Canada Research Chair in Gastrointestinal Immunology; Drs. Murray and David were supported in part by R01 DK71003.. Peer reviewed | |||||||||||||
Publication details | |||||||||||||
| |||||||||||||