TL-139-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function
TL-139-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function
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DOI：
10.1016/j.immuni.2004.06.007
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发表时间：
2004-07-01
期刊：
影响因子：
32.4
通讯作者：
Colonna, M
中科院分区：
文献类型：
--
作者：
Krug, A;French, AR;Colonna, M
天然干扰素产生细胞(IPC)通过分泌I型干扰素(干扰素)和白介素12(IL-12)来应对病毒。Toll样受体(TLR)9在体外介导IPC对其中一些病毒的识别。然而，TLR9诱导的IPC激活是否是体内有效的抗病毒反应所必需的还不清楚。在这里，我们证明了IPC和树突状细胞(DC)通过TLR9识别小鼠巨细胞病毒(MCMV)。TLR9介导的细胞因子分泌促进表达MCMV特异性受体Ly49H的NK细胞清除病毒。虽然IPC的耗尽导致干扰素-α反应的急剧减少，但这允许其他类型的细胞分泌IL-12，确保正常的干扰素-γ和NK细胞对MCMV的反应。我们得出结论，TLR9/MyD88途径通过IPC、DC和可能的其他细胞类型介导抗病毒细胞因子反应，这些细胞类型被协调以促进有效的NK细胞功能和MCMV清除。
Natural interferon-producing cells (IPC) respond to viruses by secreting type I interferon (IFN) and interleukin-12 (IL-12). Toll-like receptor (TLR) 9 mediates IPC recognition of some of these viruses in vitro. However, whether TLR9-induced activation of IPC is necessary for an effective antiviral response in vivo is not clear. Here, we demonstrate that IPC and dendritic cells (DC) recognize murine cytomegalovirus (MCMV) through TLR9. TLR9-mediated cytokine secretion promotes viral clearance by NK cells that express the MCMV-specific receptor Ly49H. Although depletion of IPC leads to a drastic reduction of the IFN-alpha response, this allows other cell types to secrete IL-12, ensuring normal IFN-gamma and NK cell responses to MCMV. We conclude that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance.