文章基本信息

标题：Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection
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作者：Ângela C. Crespo ; Jack L. Strominger ; Tamara Tilburgs 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：52
页码：15072-15077
DOI：10.1073/pnas.1617927114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe etiology of pregnancy complications such as miscarriage, preterm birth, and preeclampsia are largely unknown. The combination of the maternal Killer Immunoglobulin-like Receptor-2DS1 (KIR2DS1) with fetal HLA-C was identified as a factor determining risk of pregnancy complications. Thus decidual natural killer cells (dNK) that express high levels of KIR may have a predominant role in pregnancy outcome. Although the dNK effect has been associated with cytokine and growth factor production to promote placentation, here we show that the combination of maternal KIR and HLA-C is also a factor that determines protection against placental human cytomegalovirus (HCMV) infections. Expression of KIR2DS1 by dNK increases the cytotoxic response of dNK to HLA-C2+ HCMV-infected maternal decidual stromal cells, preventing viral spread and placental pathology. The combination of the activating killer cell Ig-like receptor 2DS1 (KIR2DS1) expressed by maternal decidual natural killer cells (dNK) and the presence of its ligand, the HLA-C allotype HLA-C2, expressed by fetal trophoblasts, reduces the risk of developing pregnancy complications. However, no molecular or cellular mechanism explains this genetic correlation. Here we demonstrate that KIR2DS1+ dNK acquired higher cytotoxic function than KIR2DS1- dNK when exposed to human cytomegalovirus (HCMV)-infected decidual stromal cells (DSC), particularly when DSCs express HLA-C2. Furthermore, dNK were unable to degranulate or secrete cytokines in response to HCMV-infected primary fetal extravillous trophoblasts. This emphasizes the immunological challenge to clear placental viral infections within the immune-privileged placenta. Activation of dNK through KIR2DS1/HLA-C2 interaction increases their ability to respond to placental HCMV infection and may limit subsequent virus-induced placental pathology. This mechanism is directly related to how KIR2DS1 expressed by dNK reduces development of severe pregnancy complications such as miscarriages and preterm delivery.
关键词：human ; HLA-C ; trophoblast ; pregnancy ; immune tolerance