Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C+ Natural Killer Cells
Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C+ Natural Killer Cells
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DOI：
10.1159/000445320
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Retiere, Christelle
中科院分区：
文献类型：
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作者：
Djaoud, Zakia;Riou, Raphaelle;Retiere, Christelle
在先天细胞中，自然杀伤细胞（NK）在防御巨细胞病毒（CMV）中起着至关重要的作用。在一些个体中，巨细胞病毒感染诱导NKG2C(+) NK细胞在感染控制后持续扩增。我们之前已经证明，与NKG2C(+) NK细胞相比，KIR2DL(+) NK细胞有助于控制CMV感染，使用CMV感染的单核细胞衍生树突状细胞（MDDC）模型。然而，cmv感染细胞促进NKG2C(+) NK细胞亚群扩增的性质尚不清楚。为了更深入地了解这个问题，我们研究了从肾移植供者中分离的cmv感染的原代人主动脉内皮细胞（EC）对NKG2C(+) NK细胞活化的贡献，这些细胞组成性地表达人白细胞抗原(HLA)-E分子。在这里，我们发现，尽管经典HLA I类表达急剧下调，但在cmv感染的EC中，非经典HLA- e表达保持不变。通过比较CMV感染的EC、成纤维细胞和MDDC中的HLA表达模式，我们证实了CMV感染对HLA- e表达的细胞依赖性调节。无论HLA-E等位基因产物的性质如何，cmv感染的EC都能显著触发NKG2C(+) NK细胞脱粒。EC主要存在于血管中，可能构成CMV感染的特权位点，驱动“记忆”NKG2C(+) NK细胞亚群。(C) 2016 S. Karger AG，巴塞尔
Among innate cells, natural killer (NK) cells play a crucial role in the defense against cytomegalovirus (CMV). In some individuals, CMV infection induces the expansion of NKG2C(+) NK cells that persist after control of the infection. We have previously shown that KIR2DL(+) NK cells, in contrast to NKG2C(+) NK cells, contribute to controlling CMV infection using a CMV-infected monocyte-derived dendritic cell (MDDC) model. However, the nature of CMV-infected cells contributing to the expansion of the NKG2C(+) NK cell subset remains unclear. To gain more insight into this question, we investigated the contribution of NKG2C(+) NK cell activation by CMV-infected primary human aortic endothelial cells (EC) isolated from kidney transplant donors, which constitutively express the human leukocyte antigen (HLA)-E molecule. Here, we show that, although classic HLA class I expression was drastically downregulated, nonclassic HLA-E expression was maintained in CMV-infected EC. By comparing HLA expression patterns in CMV-infected EC, fibroblasts and MDDC, we demonstrate a cell-dependent modulation of HLA-E expression by CMV infection. NKG2C(+) NK cell degranulation was significantly triggered by CMV-infected EC regardless of the nature of the HLA-E allele product. EC, predominantly present in vessels, may constitute a privileged site for CMV infection that drives a 'memory' NKG2C(+) NK cell subset. (C) 2016 S. Karger AG, Basel