Human placental trophoblasts confer viral resistance to recipient cells

Human placental trophoblasts confer viral resistance to recipient cells
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DOI:
10.1073/pnas.1304718110
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发表时间:
2013-07-16
影响因子:
11.1
通讯作者:
Coyne, Carolyn B.
Coyne, Carolyn B.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Delorme-Axford, Elizabeth;Donker, Rogier B.;Coyne, Carolyn B.

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胎盘滋养层形成胎儿和母体环境之间的界面,并用于限制病毒的母体-胎儿传播。在这里,我们表明培养的原代人胎盘滋养层细胞对多种病毒的感染具有高度抵抗力,重要的是,通过外泌体介导的特定微小RNA(miRNA)递送将这种抵抗力赋予非胎盘受体细胞。我们发现,染色体19 miRNA簇的miRNA成员,几乎只在人胎盘中表达,被包装在滋养层来源的外泌体中,并通过诱导自噬减弱受体细胞中的病毒复制。总之,我们的研究结果确定了胎盘滋养层的前所未有的旁分泌和/或系统功能,该功能使用外泌体介导的一组独特的胎盘特异性效应器miRNA的转移来直接与胎盘或母体靶细胞通信并调节其对病毒感染的免疫力。
Placental trophoblasts form the interface between the fetal and maternal environments and serve to limit the maternal-fetal spread of viruses. Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of viruses and, importantly, confer this resistance to nonplacental recipient cells by exosome-mediated delivery of specific microRNAs (miRNAs). We show that miRNA members of the chromosome 19 miRNA cluster, which are almost exclusively expressed in the human placenta, are packaged within trophoblast-derived exosomes and attenuate viral replication in recipient cells by the induction of autophagy. Together, our findings identify an unprecedented paracrine and/or systemic function of placental trophoblasts that uses exosome-mediated transfer of a unique set of placental-specific effector miRNAs to directly communicate with placental or maternal target cells and regulate their immunity to viral infections.