Host responses to intestinal microbial antigens in gluten-sensitive mice

• Published in: PloS one 2009-07, Vol.4 (7), p.e6472
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Animals; Antibodies; Antigens; Antigens, Bacterial - immunology; Bacteria; Cadherins - genetics; Celiac disease; Cell culture; Cell proliferation; Cytokines; E coli; E-cadherin; Electron microscopy; Environmental factors; Epithelial cells; Escherichia coli; Families & family life; Flow cytometry; Fluorescence; Fluorescence in situ hybridization; Gastroenterology and Hepatology/Small Intestine; Gene expression; Gluten; Glutens - adverse effects; Histocompatibility antigen HLA; HLA-DQ Antigens - immunology; Immune response; Immune system; Immunoglobulin M; Immunology; Indomethacin; Indomethacin - administration & dosage; Inflammatory bowel disease; Interferon; Intestinal microflora; Intestine; Intestines - microbiology; Intestines - ultrastructure; Lymphocytes T; Mathematical models; Medical research; Mice; Microbiota (Symbiotic organisms); Microorganisms; Pathology; Permeability; Physiology/Gastroenterology and Hepatology; Physiology/Immune Response; Probiotics; Proteins; Ribonucleic acid; RNA; RNA, Messenger - genetics; Rodents; Small intestine; Statistical analysis; T cells; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006472

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. 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. 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.