Human Cytomegalovirus Interacts with Toll-like Receptor 2 and CD14 on Syncytiotrophoblasts to Stimulate Expression of TNFα mRNA and Apoptosis
Human Cytomegalovirus Interacts with Toll-like Receptor 2 and CD14 on Syncytiotrophoblasts to Stimulate Expression of TNFα mRNA and Apoptosis
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DOI：
10.1016/j.placenta.2009.09.001
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发表时间：
2009-11-01
期刊：
影响因子：
3.8
通讯作者：
Guilbert, L. J.
中科院分区：
文献类型：
--
作者：
Chaudhuri, S.;Lowen, B.;Guilbert, L. J.
先天性人巨细胞病毒（HCMV）感染的新生儿胎盘通常表现为浅着床、慢性绒毛炎和合胞滋养层破坏。关于HCMV感染如何诱导胎盘炎症和滋养层细胞的丧失知之甚少。我们认为，炎症是由成熟的合体滋养层细胞（ST）对病毒的先天性防御反应引发的。先前我们已经表明，紫外线照射灭活的（UV-）HCMV与分化成ST样细胞的原代胎盘细胞滋养层（CT）上的toll样受体2（TLR 2）相互作用，从而刺激肿瘤坏死因子α（TNF α）的释放并诱导邻近细胞的凋亡（Chan等人，J.Pathol. 210：111，2006）。我们现在确定是否已知的辅助因子的相互作用的HCMV和TLR 2（TLR 1和CD 14）结合UV-HCMV刺激表达的TNF α和凋亡的ST样细胞，但不是CT。我们发现，CT都不能表达可检测到的TLR 1和表达少得多的CD 14比ST和ST表达CD 14，但不TLR 1在体内和培养的细胞。UV-HCMV和HCMV与ST样细胞表面上的CD 14的相互作用增加了TNF α的表达并诱导了群体中的凋亡。抗CD 14抗体还抑制HCMV立即早期（HCMV IE）表达ST样细胞的感染性HCMV诱导。我们的结论是，原发性绒毛CT表达低水平的CD 14和TLR 1，但ST强烈表达CD 14，其作用于TLR 2的上游，收集甚至转录无活性的病毒颗粒，以刺激TNF α表达和绒毛滋养层损伤。(C)2009爱思唯尔有限公司版权所有。
Placentae from newborns with congenital human cytomegalovirus (HCMV) infection often display shallow implantation, chronic villitis and disruptions of the syncytiotrophoblast. Little is known about how HCMV infection induces inflammation in the placenta and loss of the trophoblast. We propose that the inflammation is initiated with innate defense responses of mature syncytiotrophoblast (ST) to virus. Previously we have shown that ultraviolet irradiation-inactivated (UV-) HCMV interacts with toll-like receptor 2 (TLR2) on primary placental cytotrophoblasts (CT) differentiated into ST-like cells thereby stimulating the release of tumor necrosis factor alpha (TNF alpha) and inducing apoptosis of neighboring cells (Chan et al, J. Pathol. 210: 111, 2006). We now determine whether known co-factors of the interaction of HCMV and TLR2 (TLR1 and CD14) bind to UV-HCMV to stimulate expression of TNF alpha and apoptosis in ST-like cells but not CT. We show that CT both fail to express detectable TLR1 and express much less CD14 than ST and that ST express CD14 but not TLR1 both in vivo and in cultured cells. The interaction of UV-HCMV and HCMV with CD14 on the surface of ST-like cells increases TNF alpha expression and induces apoptosis in the population. Antibody to CD14 also inhibits infectious HCMV induction of HCMV immediate early (HCMV IE) expressing ST-like cells. We conclude that primary villous CT express low levels of CD14 and no TLR1 but that ST strongly expresses CD14 which acts upstream of TLR2 to collect even transcriptionally inactive virus particles to stimulate TNF alpha expression and villous trophoblast damage. (C) 2009 Elsevier Ltd. All rights reserved.