期刊
INFECTION AND IMMUNITY
卷 77, 期 9, 页码 3879-3885出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.01461-08
关键词
-
资金
- Wellcome Trust [055503, 62264]
To study the specific role of transmembrane tumor necrosis factor (tmTNF) in protective and pathological responses against the gastrointestinal helminth Trichinella spiralis, we compared the immune responses of TNF-alpha/lymphotoxin alpha (LT alpha)(-/-) mice expressing noncleavable transgenic tmTNF to those of TNF-alpha/LT alpha(-/-) and wild-type mice. The susceptibility of TNF-alpha/LT alpha(-/-) mice to T. spiralis infection was associated with impaired induction of a protective Th2 response and the lack of mucosal mastocytosis. Although tmTNF-expressing transgenic (tmTNF-tg) mice also had a reduced Th2 response, the mast cell response was greater than that observed in TNF-alpha/LT alpha(-/-) mice and was sufficient to induce the expulsion of the parasite. T. spiralis infection of tmTNF-tg mice resulted in significant intestinal pathology characterized by villus atrophy and crypt hyperplasia comparable to that induced following the infection of wild-type mice, while pathology in TNF-alpha/LT alpha(-/-) mice was significantly reduced. Our data thus indicate a role for tmTNF in host defense against gastrointestinal helminths and in the accompanying enteropathy. Furthermore, they also demonstrate that TNF-alpha is required for the induction of Th2 immune responses related to infection with gastrointestinal helminth parasites.
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