Divergent trophoblast responses to bacterial products mediated by TLRs
Divergent trophoblast responses to bacterial products mediated by TLRs
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DOI：
10.4049/jimmunol.173.7.4286
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发表时间：
2004-10-01
影响因子：
4.4
通讯作者：
Mor, G
中科院分区：
文献类型：
--
作者：
Abrahams, VM;Bole-Aldo, P;Mor, G
宫内感染与妊娠并发症有关，妊娠并发症也与滋养细胞凋亡增加有关。tlr是先天免疫系统的关键组成部分，它识别病原体表面的保守序列并触发效应细胞功能。我们推测宫内感染可能导致异常妊娠中观察到的滋养细胞过度凋亡，TLR可能提供了一种发病机制。在这项研究中，我们描述了TLR-2和TLR-4在妊娠早期滋养细胞中的表达和功能。虽然TLR4的连接诱导滋养细胞产生细胞因子，但TLR-2的激活诱导细胞凋亡。TLR-2介导的细胞凋亡依赖于fas相关的死亡结构域、X-finked细胞凋亡抑制剂的失活以及caspases 8、9和3的激活。这些结果提示某些宫内感染可能通过TLR-2直接诱导滋养细胞死亡。我们的发现为某些妊娠并发症的发病机制提供了一种新的机制，其中有先天免疫系统的参与。
Intrauterine infections have been associated with pregnancy complications that are also linked with increased trophoblast apoptosis. TLRs are key components of the innate immune system which recognize conserved sequences on the surface of pathogens and trigger effector cell functions. We hypothesize that intrauterine infections may cause the excessive trophoblast cell apoptosis observed in abnormal pregnancies and that TLR may provide a mechanism of pathogenesis. In this study we describe the expression and function of TLR-2 and TLR-4 in first trimester trophoblast cells. Although ligation of TLR4 induced cytokine production by trophoblast cells, TLR-2 activation induced apoptosis. TLR-2 mediated apoptosis was dependent upon the Fas-associated death domain, the inactivation of the X-finked inhibitor of apoptosis, and the activation of caspases 8, 9, and 3. These results suggest that certain intrauterine infections may directly induce trophoblast cell death through TLR-2. Our findings provide a novel mechanism of pathogenesis for certain pregnancy complications in which there is engagement of the innate immune system.