期刊
INFLAMMATORY BOWEL DISEASES
卷 16, 期 3, 页码 401-409出版社
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.21097
关键词
DSS colitis; flagellin; innate immunity
资金
- Crohn's and Colitis Foundation of Canada
- Canadian Institutes of Health Research: New Emerging Team Grants in Clinical Autoimmunity [IIN 84037]
- CIHR/MSFHR
Background: The two forms of human inflammatory bowel disease, Crohn's disease (CD) and ulcerative colitis (UC), are both associated with loss of tolerance to gut microbial antigens. The dominant antigen recognized by antibody and T-cell responses in patients with CD is bacterial flagellin. Flagellin is also the only known ligand for Toll-like receptor 5 (TLR5), a key protein in innate immunity. Although flagellin activates TLR5 to produce inflammatory responses in many cell types in the gut, there is conflicting evidence as to whether TLR5 is harmful or protective in CD and murine colitis models. A recent study found that administration of flagellin enemas to mice along with dextran sodium sulfate (DSS) made their colitis worse. Methods: We sought to determine whether this exacerbation was due to TLR5 ligation, or to TLR5-independent adaptive immune responses to flagellin as an antigen, by using a transposon insertional mutant of the Escherichia coli H18 flagellin, 2H3, which lacks TLR5 stimulatory activity. Results: We found that flagellin enemas produced only a mild exacerbation of DSS colitis, and that 2H3 was equivalent to or worse than wildtype flagellin. Moreover, we found that DSS colitis was more severe in TLR5(-/-) mice than wildtype C57BL/6 mice. Conclusions: Together, these results suggest that flagellin-mediated exacerbation of colitis is independent of TLR5.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据