Krug Anne, French Anthony R, Barchet Winfried, Fischer Jens A A, Dzionek Andrzej, Pingel Jeanette T, Orihuela Michael M, Akira Shizuo, Yokoyama Wayne M, Colonna Marco
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Immunity. 2004 Jul;21(1):107-19. doi: 10.1016/j.immuni.2004.06.007.
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.
天然干扰素产生细胞（IPC）通过分泌I型干扰素（IFN）和白细胞介素-12（IL-12）对病毒作出反应。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激活对于体内有效的抗病毒反应是否必要尚不清楚。在此，我们证明IPC和树突状细胞（DC）通过TLR9识别鼠巨细胞病毒（MCMV）。TLR9介导的细胞因子分泌促进表达MCMV特异性受体Ly49H的自然杀伤细胞（NK细胞）清除病毒。虽然IPC的耗竭导致IFN-α反应急剧降低，但这使得其他细胞类型能够分泌IL-12，确保对MCMV的正常IFN-γ和NK细胞反应。我们得出结论，TLR9/髓样分化因子88（MyD88）途径介导IPC、DC以及可能其他细胞类型的抗病毒细胞因子反应，这些反应相互协调以促进有效的NK细胞功能和MCMV清除。
