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 A Murray, Kathy D. McCoy, Elena F. Verdú

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

Fingerprint

Glutens
gluten
intestinal microorganisms
indomethacin
antigens
Antigens
Indomethacin
mice
epithelial cells
Epithelial Cells
Permeability
permeability
RNA
bacterial antigens
Bacterial Antigens
antibodies
T-cells
cadherins
Antibodies
Cell proliferation

ASJC Scopus subject areas

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

Cite this

Natividad, J. M., Huang, X., Slack, E., Jury, J., Sanz, Y., David, C., ... Verdú, E. F. (2009). Host responses to intestinal microbial antigens in gluten-sensitive mice. PLoS One, 4(7), [e6472]. https://doi.org/10.1371/journal.pone.0006472

Host responses to intestinal microbial antigens in gluten-sensitive mice. / Natividad, Jane M.; Huang, Xianxi; Slack, Emma; Jury, Jennifer; Sanz, Yolanda; David, Chella; Denou, Emmanuel; Yang, Pinchang; Murray, Joseph A; McCoy, Kathy D.; Verdú, Elena F.

In: PLoS One, Vol. 4, No. 7, e6472, 31.07.2009.

Research output: Contribution to journalArticle

Natividad, JM, Huang, X, Slack, E, Jury, J, Sanz, Y, David, C, Denou, E, Yang, P, Murray, JA, McCoy, KD & Verdú, EF 2009, 'Host responses to intestinal microbial antigens in gluten-sensitive mice', PLoS One, vol. 4, no. 7, e6472. https://doi.org/10.1371/journal.pone.0006472
Natividad JM, Huang X, Slack E, Jury J, Sanz Y, David C et al. Host responses to intestinal microbial antigens in gluten-sensitive mice. PLoS One. 2009 Jul 31;4(7). e6472. https://doi.org/10.1371/journal.pone.0006472
Natividad, Jane M. ; Huang, Xianxi ; Slack, Emma ; Jury, Jennifer ; Sanz, Yolanda ; David, Chella ; Denou, Emmanuel ; Yang, Pinchang ; Murray, Joseph A ; McCoy, Kathy D. ; Verdú, Elena F. / Host responses to intestinal microbial antigens in gluten-sensitive mice. In: PLoS One. 2009 ; Vol. 4, No. 7.
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