Increased bacterial translocation in gluten-sensitive mice is independent of small intestinal paracellular permeability defect

Manuel A. Silva, Jennifer Jury, Yolanda Sanz, Michelle Wiepjes, Xianxi Huang, Joseph A. Murray, Chella S. David, Alessio Fasano, Elena F. Verdú

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Aim: We investigated whether treatment with gliadin induces a paracellular permeability defect that enhances bacterial translocation to mesenteric lymph nodes (MLN) via resident dendritic cells (DC) expressing TLR-2 or 4 in HCD4/HLA-DQ8 transgenic mice. Methods: HLA-DQ8 transgenic mice were sensitized and subsequently gavaged with gliadin, in the presence or absence of AT1001 (paracellular permeability inhibitor). Non-sensitized mice were gavaged with indomethacin (permeability inducer) or rice cereal. CD11c and CD103 (DC markers) and TLR-2 and 4 were investigated by immunostaining. Intestinal permeability was assessed by paracellular flux of 51Cr-EDTA in Ussing chambers. Bacterial translocation to MLN was performed by plate counting on aerobic and anaerobic conditions. Results: In gliadin-treated mice, both 51Cr-EDTA flux in jejunal mucosa and aerobic and anaerobic bacterial counts in MLN were increased (p < 0.05) compared to indomethacin-treated mice and controls. The inhibitor AT1001 normalized 51Cr-EDTA flux, but had no effect on bacterial translocation in gliadin-treated mice. In addition, changes in mucosal DC marker distribution such as increased (p < 0.05) trans-epithelial CD103 + cells and reduction (p < 0.05) of CD11c immunostaining were detected in gliadin-treated mice. Moreover, changes in DC markers and TLR-2 or 4 immunophenotypes were not associated. Conclusions: Pharmacological restoration of paracellular permeability was not sufficient to prevent bacterial translocation in gluten-sensitive mice. We hypothesize that transcellular mechanisms involving CD103 +DC and CD11c +DC may explain in gluten-sensitive HCD4/HLA-DQ8 transgenic mice the sustained increased bacterial translocation observed in the absence of a significant inflammatory response.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalDigestive diseases and sciences
Volume57
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Celiac disease
  • Dendritic cells
  • HCD4/HLA-DQ8 transgenic mice
  • Intestinal permeability
  • Toll-like receptors

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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