Yu Jiabo, Sun Xiang, Goie Jian Yi Gerald, Zhang Yongliang
Integrative Biomedical Sciences Programme, University of Edinburgh Institute, Zhejiang University, International Campus Zhejiang University, Haining 314400, China.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Microorganisms. 2020 Jul 17;8(7):1067. doi: 10.3390/microorganisms8071067.
Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for the development of novel therapies for treatments. Among the multiple signal transduction pathways regulating the host immune activation and function in response to IAV infections, the mitogen-activated protein kinase (MAPK) pathways are important signalling axes, downstream of various pattern recognition receptors (PRRs), activated by IAVs that regulate various cellular processes in immune cells of both innate and adaptive immunity. Moreover, aberrant MAPK activation underpins overexuberant production of inflammatory mediators, promoting the development of the "cytokine storm", a characteristic of severe respiratory viral diseases. Therefore, elucidation of the regulatory roles of MAPK in immune responses against IAVs is not only essential for understanding the pathogenesis of severe influenza, but also critical for developing MAPK-dependent therapies for treatment of respiratory viral diseases. In this review, we will summarise the current understanding of MAPK functions in both innate and adaptive immune response against IAVs and discuss their contributions towards the cytokine storm caused by highly pathogenic influenza viruses.
流感是一种主要的呼吸道病毒性疾病，由甲型流感病毒（IAV）感染引起，每年在全球不同季节爆发。宿主免疫反应是决定流感感染疾病严重程度的关键因素，是开发新型治疗方法的一个有吸引力的靶点。在调节宿主对IAV感染的免疫激活和功能的多个信号转导途径中，丝裂原活化蛋白激酶（MAPK）途径是重要的信号轴，位于各种模式识别受体（PRR）的下游，由IAV激活，调节先天免疫和适应性免疫的免疫细胞中的各种细胞过程。此外，MAPK的异常激活是炎症介质过度产生的基础，促进了 “细胞因子风暴” 的发展，这是严重呼吸道病毒性疾病的一个特征。因此，阐明MAPK在针对IAV的免疫反应中的调节作用，不仅对于理解重症流感的发病机制至关重要，而且对于开发依赖MAPK的呼吸道病毒性疾病治疗方法也至关重要。在这篇综述中，我们将总结目前对MAPK在针对IAV的先天免疫和适应性免疫反应中的功能的理解，并讨论它们对高致病性流感病毒引起的细胞因子风暴的影响。
