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|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.|
|Publisher:||Public Library of Science|
|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|
|Citation:||PLoS ONE 4(7): e6472 (2009)|
|Appears in Collections:||(IATA) Artículos|
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