NKp46 and NKG2D recognition of infected dendritic cells is necessary for NK cell activation in the human response to influenza infection
NKp46 and NKG2D recognition of infected dendritic cells is necessary for NK cell activation in the human response to influenza infection
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DOI：
10.4049/jimmunol.178.5.2688
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Parham, Peter
中科院分区：
文献类型：
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作者：
Draghi, Monia;Pashine, Achal;Parham, Peter
在病毒感染的早期阶段，树突状细胞（DC）和NK细胞之间的接触和合作激活先天免疫，并在需要时影响适应性免疫的募集。流感是一种适应性强的快速进化病毒，每年都会引起急性、广泛的感染，挑战人类的先天和适应性免疫。在这项研究中，我们解剖和定义的分子机制，流感感染，人类树突状细胞激活静息，自体NK细胞。NK细胞活化中的三个事件显示了对由感染的DC产生的可溶性介质和与感染的DC接触产生的信号的不同要求。IFN-α主要负责增强NK细胞溶解，对CD 69上调也很重要，而IL-12是增强IFN-γ产生所必需的。增加CD 69表达和IFN-γ产生，但不增加细胞溶解，需要通过两种NK细胞受体NKG 2D和NKp 46识别流感感染的DC。对这些受体或其已知配体（NKG 2D的UL 16结合蛋白1-3 I类分子和NKp 46的流感血凝素）具有特异性的Ab可抑制CD 69表达和IFN-γ产生。流感病毒感染的DC和聚肌胞苷酸（poly（I：C））处理的DC对NK细胞的激活是不同的。Poly（I：C）处理的DC不表达NKG 2D的UL 16结合蛋白3配体，并且在不存在流感血凝素的情况下，NKp 46不参与。
At an early phase of viral infection, contact and cooperation between dendritic cells (DCs) and NK cells activates innate immunity, and also influences recruitment, when needed, of adaptive immunity. Influenza, an adaptable fast-evolving virus, annually causes acute, widespread infections that challenge the innate and adaptive immunity of humanity. In this study, we dissect and define the molecular mechanisms by which influenza-infected, human DCs activate resting, autologous NK cells. Three events in NK cell activation showed different requirements for soluble mediators made by infected DCs and for signals arising from contact with infected DCs. IFN-alpha was mainly responsible for enhanced NK cytolysis and also important for CD69 up-regulation, whereas IL-12 was necessary for enhancing IFN-gamma production. Increased CD69 expression and IFN-gamma production, but not increased cytolysis, required recognition of influenza-infected DCs by two NK cell receptors: NKG2D and NKp46. Abs specific for these receptors or their known ligands (UL16-binding proteins 1-3 class I-like molecules for NKG2D and influenza hemagglutinin for NKp46) inhibited CD69 expression and IFN-gamma production. Activation of NK cells by influenza-infected DCs and polyinosinic:polycytidylic acid (poly(I:C) -treated DCs was distinguished. Poly(I:C)-treated DCs did not express the UL16-binding protein 3 ligand for NKG2D, and in the absence of the influenza hemagglutinin there was no involvement of NKp46.