Skin-stage schistosomula of Schistosoma mansoni produce an apoptosis-inducing factor that can cause apoptosis of T cells

被引:58
作者
Chen, L
Rao, KVN
He, YX
Ramaswamy, K
机构
[1] Univ Illinois, Coll Med, Dept Biomed Sci, Rockford, IL 61107 USA
[2] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
关键词
D O I
10.1074/jbc.M201344200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Skin-stage schistosomula of Schistosoma mansoni were found to secrete molecules that are pro-apoptotic for skin T lymphocytes as measured by annexin V staining, caspase-3 activity, caspase-8 activities, and DNA fragmentation. Caspase-8 activities in lymphocytes peaked similar to8 h and caspase-3 activity peaked similar to16 h after exposure to the parasite secretions. Subset analysis showed that mainly CD4(+) and CD8(+) cells (but not B cells) were susceptible to the parasite-induced proapoptotic effect. In situ staining confirmed the presence of apoptotic T cells around challenge parasites in the skin of naive or immunized animals. Analysis of T cells to identify the potential molecular pathway of the parasite-induced apoptosis showed increases in the expression of Fas, FasL, and the Fas-associated death domain. Blocking of FasL with a fusion protein reversed the parasite-induced apoptosis, suggesting a role for the Fas/FasL-mediated pathway in the parasite-induced T cell apoptosis. Subsequent analyses of the secretions of skin-stage schistosomula identified the pro-apoptotic activity as being associated with a protein of similar to23 kDa. This protein was termed S. mansoni-derived apoptosis-inducing factor.
引用
收藏
页码:34329 / 34335
页数:7
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