Department of Molecular Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy.
Department of Molecular Medicine, Istituto Pasteur Fondazione Cenci Bolognetti, "Sapienza" University of Rome, Italy; IRCCS, Neuromed, Pozzilli, IS, Italy.
Cytokine Growth Factor Rev. 2015 Apr;26(2):113-20. doi: 10.1016/j.cytogfr.2014.11.003. Epub 2014 Nov 13.
The role of Natural Killer cells in host defense against infections as well as in tumour surveillance has been widely appreciated for a number of years. Upon recognition of "altered" cells, NK cells release the content of cytolytic granules, leading to the death of target cells. Moreover, NK cells are powerful producers of chemokines and cytokines, particularly Interferon-γ (IFN-γ), of which they are the earliest source upon a variety of infections. Despite being armed to fight against pathogens, NK cells become fully functional upon an initial phase of activation that requires the action of several cytokines, including type I IFNs. Type I IFNs are now recognized as key players in antiviral defense and immune regulation, and evidences from both mouse models of disease and in vitro studies support the existence of an alliance between type I IFNs and NK cells to ensure effective protection against viral infections. This review will focus on the role of type I IFNs in regulating NK cell functions to elicit antiviral response and on NK cell-produced IFN-γ beneficial and pathological effects.
自然杀伤 (NK) 细胞在宿主抗感染防御以及肿瘤监视中的作用已被广泛认识多年。在识别“异常”细胞后,NK 细胞会释放细胞毒性颗粒的内容物,导致靶细胞死亡。此外,NK 细胞是趋化因子和细胞因子(尤其是干扰素-γ (IFN-γ))的强大产生者,它们是多种感染后最早的 IFN-γ来源。尽管 NK 细胞已准备好与病原体作斗争,但它们在初始激活阶段仍需多种细胞因子(包括 I 型 IFNs)的作用才能充分发挥功能。I 型 IFNs 现已被认为是抗病毒防御和免疫调节的关键因素,来自疾病的小鼠模型和体外研究的证据支持 I 型 IFNs 和 NK 细胞之间存在联盟,以确保对病毒感染的有效保护。本综述将重点介绍 I 型 IFNs 在调节 NK 细胞功能以引发抗病毒反应方面的作用,以及 NK 细胞产生的 IFN-γ 的有益和病理作用。