Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR41
Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR41
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DOI：
10.4049/jimmunol.177.2.1257
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发表时间：
2006-07-15
影响因子：
4.4
通讯作者：
Hobel, Calvin J.
中科院分区：
文献类型：
--
作者：
Equils, Ozlem;Lu, Daning;Hobel, Calvin J.
宫内感染影响胎盘的发育和功能，随后可能导致并发症，如早产，宫内发育迟缓和先兆子痫;然而，分子机制尚不清楚。TLRs介导胎盘的先天性免疫反应，最近，TLR 2诱导的滋养层细胞凋亡已被认为在感染诱导的早产中发挥作用。沙眼衣原体是美国最流行的性传播细菌感染的病原体。在这项研究中，我们表明，在体外衣原体热休克蛋白60诱导原代人滋养层细胞，胎盘成纤维细胞，和JEG 3滋养层细胞系的细胞凋亡，TLR 4介导这一事件。我们观察到宿主细胞类型依赖性凋亡反应。在原代胎盘成纤维细胞中，衣原体热休克蛋白60诱导的细胞凋亡是半胱天冬酶依赖的，而在JEG 3滋养层细胞系中，它是半胱天冬酶独立的。这些数据表明，TLR 4刺激诱导胎盘细胞凋亡，这可能提供了一个新的机制，为妇女的生育能力和妊娠结局差的持续衣原体感染。
Intrauterine infection affects placental development and function, and subsequently may lead to complications such as preterm delivery, intrauterine growth retardation, and preeclampsia; however, the molecular mechanisms are not clearly known. TLRs mediate innate immune responses in placenta, and recently, TLR2-induced trophoblast apoptosis has been suggested to play a role in infection-induced preterm delivery. Chlamydia trachomatis is the etiological agent of the most prevalent sexually transmitted bacterial infection in the United States. In this study, we show that in vitro chlamydial heat shock protein 60 induces apoptosis in primary human trophoblasts, placental fibroblasts, and the JEG3 trophoblast cell line, and that TLR4 mediates this event. We observed a host cell type-dependent apoptotic response. In primary placental fibroblasts, chlamydial heat shock protein 60-induced apoptosis was caspase dependent, whereas in JEG3 trophoblast cell lines it was caspase independent. These data suggest that TLR4 stimulation induces apoptosis in placenta, and this could provide a novel mechanism of pathogenesis for poor fertility and pregnancy outcome in women with persistent chlamydia infection.