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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells.
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CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells.

机译：CpG和双链RNA通过Toll样受体触发人NK细胞：诱导细胞因子释放以及对肿瘤和树突状细胞的细胞毒性。

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Toll-like receptors (TLRs) are pattern-recognition receptors responsible for triggering cells of innate immunity. In this study we investigated the expression and function of TLRs 3 and 9 in human natural killer (NK) cells. In the presence of IL-12, freshly isolated NK cells responded to double-stranded RNA or unmethylated CpG DNA and expressed CD69 and CD25 activation markers. Because both markers were expressed by virtually all NK cells, this would suggest that most of them can be triggered by TLRs. Remarkably, NK cell stimulation also resulted in the induction of their functional program as revealed by IFN-gamma and tumor necrosis factor-alpha release and by up-regulation of cytolytic activity against tumor cells. IL-8 could efficiently substitute IL-12 in supporting NK cell responses to TLR-mediated stimulation. Importantly, freshly isolated NK cells acquired the ability to lyse immature dendritic cells after stimulation with double-stranded RNA and IL-12. However, responses to these stimuli were not restricted to fresh NK cells, because significant responses were also detected in polyclonal NK cells cultured in the presence of exogenous IL-2 for several weeks. The analysis of NK cell clones revealed some degree of heterogeneity in the ability to respond to TLR stimulation also among NK clones derived from a single donor. These data suggest that stimuli acting on TLR not only activate immature dendritic cells to release IL-12 but also render NK cells capable of receiving triggering signals from pathogen-associated molecules, thus exerting a regulatory control on the early steps of innate immune responses against infectious agents.
机译：Toll样受体（TLR）是负责触发先天免疫细胞的模式识别受体。在这项研究中，我们调查了人类自然杀伤（NK）细胞中TLR 3和9的表达和功能。在存在IL-12的情况下，新鲜分离的NK细胞对双链RNA或未甲基化的CpG DNA作出反应，并表达CD69和CD25激活标记。因为这两种标记实际上都是由所有NK细胞表达的，这表明它们大多数都可以由TLR触发。值得注意的是，NK细胞刺激还导致其功能程序的诱导，如IFN-γ和肿瘤坏死因子-α释放以及上调针对肿瘤细胞的溶细胞活性所揭示的。 IL-8在支持NK细胞对TLR介导的刺激的反应中可以有效替代IL-12。重要的是，在用双链RNA和IL-12刺激后，新鲜分离的NK细胞具有裂解未成熟树突状细胞的能力。然而，对这些刺激的反应并不限于新鲜的NK细胞，因为在存在外源IL-2的情况下培养了数周的多克隆NK细胞中也检测到了显着的反应。 NK细胞克隆的分析显示，在源自单个供体的NK克隆中，对TLR刺激的反应能力也存在一定程度的异质性。这些数据表明，作用于TLR的刺激不仅激活未成熟的树突状细胞释放IL-12，而且使NK细胞能够接收来自病原体相关分子的触发信号，从而在针对感染的先天免疫应答的早期步骤中发挥了调控作用。代理商。

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