Gram-negative commensal gut bacteria aggravate small intestinal inflammation via toll-like receptor 4
Abstract number: p1189
Heimesaat M.M., Fischer A., Jahn H.-K., Niebergall J., Liesenfeld O., Schumann R.R., Bereswill S., Göbel U.B.
Gram-negative commensal gut bacteria such as Escherichia coli and Bacteroides sp. are suspected to contribute profoundly to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. It has been recently shown that both bacterial groups accumulate at very high levels in the inflamed ileum and trigger severe Th1-type immunopathology of acute pan-ileitis in susceptible mice infected perorally with 100 cysts of Toxoplasma gondii. Thus, this model is excellently suited for the study of host-bacterial-relationships in small intestinal inflammation. To unravel the mechanisms by which bacteria aggravate ileal inflammation, we investigated the severity of small intestinal inflammation in mice lacking Toll-like receptors (TLRs) 2 and 4, which constitute important components of the bacteria-related innate immune system. Escherichia coli and Bacteroides sp. accumulated to comparable levels during ileitis and their concentrations did not differ significantly in inflamed ilea of wild type mice and of mice lacking TLR2 or TLR4. However, the severity of ileitis was clearly diminished in mice lacking TLR4-/-, as indicated by reduced histological scores and letality. Because TLR4 is highly specific for bacterial lipopolysaccharide (LPS), these findings provide evidence that commensal gut bacteria aggravate the immunopathology of intestinal inflammation via TLR4-mediated sensing of bacterial LPS, which might play a key role in inflammatory process.
|Session name:||XXIst ISTH Congress|
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