Toll-like receptor 2 plays a critical role in maintaining mucosal integrity during Citrobacter rodentium-induced colitis

被引:138
作者
Gibson, Deanna L. [1 ]
Ma, Caixia [1 ]
Rosenberger, Carrie M. [3 ]
Bergstrom, Kirk S. B. [1 ]
Valdez, Yanet [2 ]
Huang, Jingtian T. [1 ]
Khan, Mohammed A. [1 ]
Vallance, Bruce A. [1 ]
机构
[1] Univ British Columbia, Div Gastroenterol, BC Childrens Hosp, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada
[3] Inst Syst Biol, Seattle, WA USA
关键词
D O I
10.1111/j.1462-5822.2007.01052.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Inflammatory bowel diseases and infectious gastroenteritis likely occur when the integrity of intestinal barriers is disrupted allowing luminal bacterial products to cross into the intestinal mucosa, stimulating immune cells and triggering inflammation. While specific Toll-like receptors (TLR) are involved in the generation of inflammatory responses against enteric bacteria, their contributions to the maintenance of intestinal mucosal integrity are less clear. These studies investigated the role of TLR2 in a model of murine colitis induced by the bacterial pathogen Citrobacter rodentium. C. rodentium supernatants specifically activated TLR2 in vitro while infected TLR2-/- mice suffered a lethal colitis coincident with colonic mucosal ulcerations, bleeding and increased cell death but not increased pathogen burden. TLR2-/- mice suffered impaired epithelial barrier function mediated via zonula occludens (ZO)-1 in naive mice and claudin-3 in infected mice, suggesting this could underlie their susceptibility. TLR2 deficiency was also associated with impaired production of IL-6 by bone marrow-derived macrophages and infected colons cultured ex vivo. As IL-6 has antiapoptotic and epithelial repair capabilities, its reduced expression could contribute to the impaired mucosal integrity. These studies report for the first time that TLR2 plays a critical role in maintaining intestinal mucosal integrity during infection by a bacterial pathogen.
引用
收藏
页码:388 / 403
页数:16
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