Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
J Innate Immun. 2011;3(3):264-73. doi: 10.1159/000326891. Epub 2011 Mar 29.
Recent progress in understanding the outcomes of pattern-recognition by myeloid dendritic cells (mDC) allows us to delineate the pathways driving natural killer (NK) cell activation. Mouse mDC mature in response to microbial patterns and are converted to an NK cell-activating phenotype. The MyD88 pathway, the Toll/IL-1 receptor homology domain-containing adaptor molecule (TICAM)-1 (TRIF) pathway, and the interferon (IFN)-β promoter stimulator 1 (IPS-1) pathway in mDC participate in driving NK activation, as shown by analyses in knockout mice. Studies using synthetic compounds for Toll-like receptors/RIG-I-like receptors have demonstrated that mDC-NK cell contact induces NK cell activation without the participation of cytokines in mice. In vivo bone marrow transplantation analysis revealed that the IPS-1 pathway in nonmyeloid cells and the TICAM-1 pathway in mDC are crucial for dsRNA-mediated in vivo NK activation. These results infer the presence of cytokine-dependent and cytokine-independent modes of NK activation in conjunction with innate immune activation. Here, we focus on the IFN-inducing pathways and mDC-NK contact-induced NK activation and discuss the reported various NK activation modes.
最近在理解髓样树突状细胞（mDC）模式识别结果方面的进展，使我们能够描绘出驱动自然杀伤（NK）细胞激活的途径。小鼠 mDC 对微生物模式作出反应而成熟，并转化为一种能够激活 NK 细胞的表型。MyD88 途径、Toll/IL-1 受体同源结构域包含衔接分子（TICAM）-1（TRIF）途径和干扰素（IFN）-β 启动子刺激物 1（IPS-1）途径在 mDC 中参与驱动 NK 激活，这在敲除小鼠的分析中得到了证实。使用 Toll 样受体/RIG-I 样受体的合成化合物进行的研究表明，在小鼠中，mDC-NK 细胞接触诱导 NK 细胞激活而无需细胞因子的参与。体内骨髓移植分析显示，非髓样细胞中的 IPS-1 途径和 mDC 中的 TICAM-1 途径对于 dsRNA 介导的体内 NK 激活至关重要。这些结果推断出与先天免疫激活相关的存在细胞因子依赖和细胞因子非依赖的 NK 激活模式。在这里，我们重点关注 IFN 诱导途径和 mDC-NK 接触诱导的 NK 激活，并讨论报告的各种 NK 激活模式。
