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Dig Dis Sci. 2012 Jan;57(1):38-47. doi: 10.1007/s10620-011-1847-z. Epub 2011 Aug 7.

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

Author information

1
Department of Medicine, Health Sciences Centre, Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. msilvamu@hotmail.com

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 (51)Cr-EDTA in Ussing chambers. Bacterial translocation to MLN was performed by plate counting on aerobic and anaerobic conditions.

RESULTS:

In gliadin-treated mice, both (51)Cr-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 (51)Cr-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.

PMID:
21822909
PMCID:
PMC3507358
DOI:
10.1007/s10620-011-1847-z
[Indexed for MEDLINE]
Free PMC Article
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