Caspase-dependent apoptosis during infection with Cryptosporidium parvum

Caspase-dependent apoptosis during infection with Cryptosporidium parvum
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DOI:
10.1016/s1286-4579(99)00246-4
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发表时间:
1999-12-01
影响因子:
5.8
通讯作者:
Laurent, F
Laurent, F
中科院分区:
医学3区
文献类型:
--
作者:
Ojcius, DM;Perfettini, JL;Laurent, F

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原生动物寄生虫微小隐孢子虫(Cryptosporidium parvum)会导致儿童持续腹泻和营养不良,并导致艾滋病患者的疟疾消耗综合征。在没有健康免疫反应的情况下,没有消除寄生虫的疗法。虽然已有报道,用C.尽管小孢子虫导致宿主细胞死亡,但细胞溶解的机制尚未被表征。我们在这里表明,感染C,小导致典型的凋亡核凝聚和宿主细胞中的DNA片段化。细胞核凝聚和DNA片段化都受到半胱天冬酶抑制剂的抑制,表明半胱天冬酶参与了这种类型的细胞凋亡。最后,用半胱天冬酶抑制剂阻断细胞凋亡增加了感染细胞的百分比,表明寄生虫可能利用细胞凋亡从感染细胞中退出,或者感染细胞可能通过细胞凋亡消除寄生虫。提示细胞凋亡可能参与了C.在体内的微小感染,并提出了可能性,治疗干扰宿主细胞死亡可以改变体内的病理过程。(C)1999年科学与医学版Elsevier SAS。
The protozoan parasite Cryptosporidium parvum causes persistent diarrhea and malnutrition in children and the diarrhea-wasting syndrome in AIDS. No therapy exists for eliminating the parasite in the absence of a healthy immune response. Although it had been reported that infection of intestinal cell lines with C. parvum leads to host cell death, the mechanisms of cytolysis have not been characterized. We show here that infection with C, parvum leads to typical apoptotic nuclear condensation and DNA fragmentation in host cells. Both nuclear condensation and DNA fragmentation are inhibited by a caspase inhibitor, showing that caspases are involved in this type of apoptosis. Finally, blocking apoptosis with the caspase inhibitor increases the percentage of infected cells, suggesting that parasites may use apoptosis to exit from the infected cell or that the infected cells may eliminate the parasite through apoptosis. These results suggest that apoptosis could be involved in the pathogenesis of C. parvum infections in vivo, and raise the possibility that therapeutic interference with host cell death could alter the course of the pathology in vivo. (C) 1999 Editions scientifiques et medicales Elsevier SAS.