Coordinate expression of cytokines and chemokines by NK cells during murine cytomegalovirus infection
Coordinate expression of cytokines and chemokines by NK cells during murine cytomegalovirus infection
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DOI：
10.4049/jimmunol.172.5.3119
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Yokoyama, WM
中科院分区：
文献类型：
--
作者：
Dorner, BG;Smith, HRC;Yokoyama, WM
细胞因子和趋化因子在感染过程中激活并引导效应细胞。我们先前鉴定了一个由五种细胞因子和趋化因子组成的功能组，即IFN-γ、活化诱导的T细胞衍生的和趋化因子相关的细胞因子/趋化因子、巨噬细胞炎性蛋白1 α、巨噬细胞炎性蛋白1 β和RANTES，它们在体外和体内感染过程中在单个活化的NK细胞、CD 8（+）T细胞和CD 4（+）Th 1细胞中共表达。然而，在感染过程中的刺激是未知的。在小鼠CMV（MCMV）感染中，DAP 12/KARAP相关的Ly 49 H NK细胞活化受体通过识别MCMV编码的m157对耐药性至关重要，但NK细胞也会对未表征的刺激物发生体内非特异性反应。在这项研究中，我们表明，通过m157连接Ly 49 H导致Ly 49 H（+）NK细胞协调释放所有五种细胞因子/趋化因子。尽管其他细胞因子也触发了这些细胞因子/趋化因子的释放，但刺激并不局限于Ly 49 H（+）群体。在单细胞水平上，5种介质的产生表现出很强的正相关性。有趣的是，NK细胞是体外和体内这五种细胞因子/趋化因子的主要来源，而感染的巨噬细胞仅产生有限数量的巨噬细胞炎性蛋白1 α、巨噬细胞炎性蛋白1 β和RANTES。这些发现表明，病毒特异性和非特异性NK细胞在MCMV感染期间激活和引导其他炎症细胞方面发挥着至关重要的作用。
Cytokines and chemokines activate and direct effector cells during infection. We previously identified a functional group of five cytokines and chemokines, namely, IFN-gamma, activation-induced T cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein 1beta, and RANTES, coexpressed in individual activated NK cells, CD8(+) T cells, and CD4(+) Th1 cells in vitro and during in vivo infections. However, the stimuli during infection were not known. In murine CMV (MCMV) infection, the DAP12/KARAP-associated Ly49H NK cell activation receptor is crucial for resistance through recognition of MCMV-encoded m157 but NK cells also undergo in vivo nonspecific responses to uncharacterized stimuli. In this study, we show that Ly49H ligation by m157 resulted in a coordinated release of all five cytokines/ chemokines from Ly49H(+) NK cells. Whereas other cytokines also triggered the release of these cytokines/chemokines, stimulation was not confined to the Ly49H(+) population. At the single-cell level, the production of the five mediators showed strong positive correlation with each other. Interestingly, NK cells were a major source of these five cytokines/chemokines in vitro and in vivo, whereas infected macrophages produced only limited amounts of macrophage-inflammatory protein 1alpha, macrophage-inflammatory protein1beta, and RANTES. These findings suggest that both virus-specific and nonspecific NK cells play crucial roles in activating and directing other inflammatory cells during MCMV infection.