Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection
Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection
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DOI：
10.1073/pnas.1617927114
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发表时间：
2016-12-27
影响因子：
11.1
通讯作者：
Tilburgs, Tamara
中科院分区：
文献类型：
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作者：
Crespo, Angela C.;Strominger, Jack L.;Tilburgs, Tamara
由母体蜕膜自然杀伤细胞（dNK）表达的活化性杀伤细胞Ig样受体2DS 1（KIR 2DS 1）与其配体（由胎儿滋养层细胞表达的HLA-C同种异型HLA-C2）的存在相结合，降低了发生妊娠并发症的风险。然而，没有分子或细胞机制解释这种遗传相关性。因此，我们证明，当暴露于人巨细胞病毒（HCMV）感染的蜕膜基质细胞（DSC）时，特别是当DSC表达HLA-C2时，KIR 2DS 1 + dNK获得比KIR 2DS 1-dNK更高的细胞毒性功能。此外，dNK细胞不能清除或分泌细胞因子，以应对HCMV感染的原代胎儿绒毛外滋养层细胞。这强调了在免疫豁免胎盘内清除胎盘病毒感染的免疫挑战。通过KIR 2DS 1/HLA-C2相互作用激活dNK增加了它们对胎盘HCMV感染的反应能力，并可能限制随后的病毒诱导的胎盘病理学。这种机制与dNK表达的KIR 2DS 1如何减少严重妊娠并发症如流产和早产的发生直接相关。
The combination of the activating killer cell Ig-like receptor 2DS1 (KIR2DS1) expressed bymaternal 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. Herewe 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.