An increase in epithelial cell apoptosis is associated with chronic intestinal nematode infection

被引:42
作者
Cliffe, Laura J.
Potten, Christopher S.
Booth, Catherine E.
Grencis, Richard K.
机构
[1] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
[2] Epistem Ltd, Manchester M13 9XX, Lancs, England
基金
英国惠康基金;
关键词
D O I
10.1128/IAI.01375-06
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It is well established that homeostasis of the intestinal epithelium becomes dysregulated during gastrointestinal helminth infection and is under immune control. An increase in both enterocyte proliferation and the subsequent generation of crypt hyperplasia are hallmarks of chronic infection with Trichuris muris, a large intestinal dwelling nematode. The effect of this parasitic infection on apoptosis induction in the large intestine and its regulation has been neglected. To address this, mice of resistant and susceptible phenotypes were infected with different doses of T. muris, and the levels of epithelial cell apoptosis were determined. It is clear that apoptosis is induced during chronic T. muris infection. This occurs mainly at the base of the cecal crypt, within the stem cell region. The level of apoptosis induced is independent of worm number, suggesting that it is not a consequence of worm-induced damage but rather a mechanism for controlling cell number within the crypt. Neutralization of both gamma interferon and tumor necrosis factor alpha caused a significant reduction in the levels of apoptosis, showing that proinflammatory cytokines generated in response to chronic infection play an important role in apoptosis induction in this system. It is proposed that the generation of proinflammatory cytokines during chronic T. muris infection may play a positive role, by promoting intestinal epithelial cell apoptosis, to counter infection-induced epithelial hyperplasia.
引用
收藏
页码:1556 / 1564
页数:9
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