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ROLE OF TLR-2 IN ILEAL DENDRITIC CELL REDISTRIBUTION FOLLOWING EPITHELIAL BARRIER DYSFUNCTION INDUCED BY INFLAMMATION IN THE RAT

MA Silva, J Jury, MH Perdue
Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario

We examined ileal dendritic cells (DC) in rats to investigate changes in distribution associated with increased epithelial permeability during early stages of gut inflammation.
METHODS: Sprague-Dawley rats were injected with indomethacin, 48h apart, and euthanized at 2, 6, 12 or 24h after treatment. To determine the role of Toll-like receptor 2 (TLR-2) in DC redistribution, additional rats were injected with anti-TLR-2 antibody. Control rats were treated with saline. Ileal sections were processed to measure inflammation by macroscopic and microscopy scores, DC distribution by immunohistochemistry, changes in intestinal epithelial permeability in Ussing chambers, epithelial damage by electronmicroscopy and bacterial adherence/penetration by aerobic/anaerobic culture.
RESULTS: In controls, CD103⁺ immature DC were mainly located in the lamina propria (LP) and some expressed TLR-2. In indomethacin-treated rats, inflammation and transfer of CD103⁺DC from LP to Peyer's patches were evident at 6-24h after treatment. TLR-2⁺DC depletion from LP was observed at 24h. Increased epithelial permeability was significant at 24h, but open tight junctions and increased enteric bacterial adherence/penetration occurred at 2 and 6h. In addition, TLR-2 blockade induced an increase in LP CD103⁺DC associated with bacterial adhesion/penetration (P<0.05).
CONCLUSIONS: Indomethacin-induced ileitis was initiated by epithelial damage and abnormal bacterial infiltration, followed by redistribution of ileal DC with depletion of TLR-2⁺DC. It is likely that DC redistribution depends on TLR-2 recognition, which may be crucial for DC activation by bacterial antigens during the pathogenesis of intestinal inflammation.

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