Lee Amanda J, Chen Branson, Chew Marianne V, Barra Nicole G, Shenouda Mira M, Nham Tina, van Rooijen Nico, Jordana Manel, Mossman Karen L, Schreiber Robert D, Mack Matthias, Ashkar Ali A
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Department of Molecular Cell Biology, Vrije University Medical Center, 1081 HV Amsterdam, Netherlands.
J Exp Med. 2017 Apr 3;214(4):1153-1167. doi: 10.1084/jem.20160880. Epub 2017 Mar 6.
The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, and mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell-derived IFN-γ. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response.
I型干扰素（IFN）在自然杀伤（NK）细胞响应病毒感染时的激活作用已为人所知，但其潜在机制仍不清楚。在此，我们证明，炎症单核细胞中的I型干扰素信号传导，而非树突状细胞（DC）或NK细胞中的信号传导，对于NK细胞在响应黏膜单纯疱疹病毒2型（HSV-2）感染时的功能至关重要。缺乏I型干扰素信号传导的小鼠以及[此处原文可能缺失特定小鼠类型信息]小鼠，炎症单核细胞水平显著降低，IL-18产生不足，且缺乏NK细胞衍生的IFN-γ。耗尽炎症单核细胞而非DC或其他髓样细胞，会导致IL-18水平降低，并在HSV-2感染中完全消除NK细胞功能。此外，这导致对HSV-2感染的易感性增加。尽管[此处原文可能缺失特定小鼠类型信息]小鼠的炎症单核细胞水平正常，但其NK细胞对HSV-2攻击无反应。本研究强调了I型干扰素信号传导在炎症单核细胞中的重要性以及早期先天性抗病毒反应的诱导。
