Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Front Immunol. 2020 Sep 25;11:558341. doi: 10.3389/fimmu.2020.558341. eCollection 2020.
The host immune system has multiple innate immune receptors that can identify, distinguish and react to viral infections. In innate immune response, the host recognizes pathogen-associated molecular patterns (PAMP) in nucleic acids or viral proteins through pathogen recognition receptors (PRRs), especially toll-like receptors (TLRs) and induces immune cells or infected cells to produce type I Interferons (IFN-I) and pro-inflammatory cytokines, thus when the virus invades the host, innate immunity is the earliest immune mechanism. Besides, cytokine-mediated cell communication is necessary for the proper regulation of immune responses. Therefore, the appropriate activation of innate immunity is necessary for the normal life activities of cells. The suppressor of the cytokine signaling proteins (SOCS) family is one of the main regulators of the innate immune response induced by microbial pathogens. They mainly participate in the negative feedback regulation of cytokine signal transduction through Janus kinase signal transducer and transcriptional activator (JAK/STAT) and other signal pathways. Taken together, this paper reviews the SOCS proteins structures and the function of each domain, as well as the latest knowledge of the role of SOCS proteins in innate immune caused by viral infections and the mechanisms by which SOCS proteins assist viruses to escape host innate immunity. Finally, we discuss potential values of these proteins in future targeted therapies.
宿主免疫系统具有多种先天免疫受体,能够识别、区分和应对病毒感染。在先天免疫反应中,宿主通过病原体识别受体(PRRs),特别是 Toll 样受体(TLRs),识别核酸或病毒蛋白中的病原体相关分子模式(PAMP),并诱导免疫细胞或受感染细胞产生 I 型干扰素(IFN-I)和促炎细胞因子,因此,当病毒侵入宿主时,先天免疫是最早的免疫机制。此外,细胞因子介导的细胞通讯对于免疫反应的适当调节是必要的。因此,适当激活先天免疫对于细胞的正常生命活动是必要的。细胞因子信号转导抑制蛋白(SOCS)家族是微生物病原体诱导的先天免疫反应的主要调节因子之一。它们主要通过 Janus 激酶信号转导物和转录激活物(JAK/STAT)和其他信号通路参与细胞因子信号转导的负反馈调节。总之,本文综述了 SOCS 蛋白的结构和各结构域的功能,以及 SOCS 蛋白在病毒感染引起的先天免疫中的作用及其协助病毒逃避宿主先天免疫的机制。最后,我们讨论了这些蛋白在未来靶向治疗中的潜在价值。