Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis
Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis
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DOI：
10.2353/ajpath.2006.050482
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发表时间：
2006-04-01
影响因子：
6
通讯作者：
Pereira, L
中科院分区：
文献类型：
--
作者：
Maidji, E;McDonagh, S;Pereira, L
人类巨细胞病毒 (CMV) 如何通过胎盘到达胎儿尚不清楚。 CMV 是先天性疾病的主要病毒原因，它会感染子宫胎盘界面，根据母体体液免疫的强度和胎龄，产生不同的结果。覆盖在血液中漂浮的绒毛表面，合体滋养层；表达新生儿 Fc 受体 (FcRn)，可转运 IgG 以实现被动免疫。早期妊娠活检标本的免疫组织化学分析显示，绒毛细胞滋养层中的 CMV 复制蛋白存在异常模式，而合体滋养层则幸免于难。在具有低至中等 CMV 中和抗体滴度的胎盘中发现，这种模式表明病毒颗粒在表面发生转胞吞作用。相反，来自具有高中和滴度的胎盘的合体滋养层含有病毒DNA和caveolin-1阳性囊泡，其中IgG和CMV糖蛋白B共定位。在绒毛外植体中，胰蛋白酶处理和可溶性蛋白 A 阻断 IgG 病毒颗粒转胞吞作用和巨噬细胞摄取。极化上皮细胞中的定量分析表明，FcRn 介导的转胞吞作用被 IgG 的 Fc 片段阻断，但 F(ab')(2) 没有阻断。我们的结果表明，CMV 病毒体可以通过选择受体介导的 IgG 转运途径传播到胎盘。这些发现可以解释超免疫 IgG 在治疗妊娠期间原发性 CMV 感染和支持疫苗接种方面的功效。
How human cytomegalovirus (CMV) reaches the fetus across the placenta is unknown. The major viral cause of congenital disease, CMV infects the uterine-placental interface with varied outcomes depending on the strength of maternal humoral immunity and gestational age. Covering the surface of villi that float in blood, syncytiotrophoblasts; express the neonatal Fc receptor (FcRn) that transports IgG for passive immunity. Immunohistochemical analysis of early-gestation biopsy specimens showed an unusual pattern of CMV replication proteins in underlying villus cytotrophoblasts, whereas syncytiotrophoblasts were spared. Found in placentas with low to moderate CMV-neutralizing antibody titers, this pattern suggested virion transcytosis across the surface. In contrast, syncytiotrophoblasts from placentas with high neutralizing titers contained viral DNA and caveolin-l-positive vesicles in which IgG and CMV glycoprotein B co-localized. In villus explants, IgG-virion transcytosis and macrophage uptake were blocked with trypsin-treatment and soluble protein A. Quantitative analysis in polarized epithelial cells showed that FcRn-mediated transcytosis was blocked by the Fc fragment of IgG, but not F(ab')(2). Our results suggest that CMV virions could disseminate to the placenta by co-opting the receptor-mediated transport pathway for IgG. These findings could explain the efficacy of hyperimmune IgG for treatment of primary CMV infection during gestation and support vaccination.