ZBP1与病原感染免疫调控研究进展

Research Progress on the Immune Regulation of ZBP1 and Patho-genic Infection

先天免疫的核心是细胞质和膜相关受体对病原体相关分子模式的感知。由于感染或细胞损伤衍生的核酸,暴露在细胞质中时都会引起免疫反应。除了经典的RNA传感机制,DNA传感系统的研究也逐步深入。其中,ZDNA结合蛋白1(ZBP1)是一种新发现的胞质核酸免疫传感器,以正反馈的方式与宿主I型IFN信号相互调节,放大先天免疫信号。ZBP1还通过特殊的结构域与异常积累的Z型核酸特异性结合,激发坏死性凋亡,促进细胞发生程序性死亡以抵御病原微生物入侵,在天然免疫应答中发挥不可或缺的作用。本综述总结了目前ZBP1蛋白参与的生理、病理作用,并着重阐述ZBP1在抵抗病原侵袭中的引起的保护性和病理性免疫调控作用,旨在为该蛋白未来的生物学功能研究提供新思路。

The core of innate immunity is the perception of pathogen-associated molecular patterns by cytoplasmic and membrane-associated receptors.Nucleic acids derived from infection or cell damage can cause an immune response if exposed to the cytoplasm.In addition to the classical mechanism of RNA sensing,research on the DNA-sensing system has also deepened gradually.Z-DNA binding protein 1(ZBP1)is a recently discovered cytosolic immunosensor of nucleic acids that positively regulates host type-I interferon signals in a feedback loop,thereby amplifying the innate immune response.ZBP1 also plays an essential part in the innate immune response.ZBP1 binds specifically to the aberrantly accumulated Z-nucleic-acid through a special domain to stimulate necroptosis and promote programmed cell death to resist the invasion of pathogenic microorganisms.This review summarizes the physiological and pathological effects of ZBP1 protein.We focus on the protective and pathological immunoregulatory effects of ZBP1 in resistance to pathogen invasion.Our review provides new ideas for future research into the biological function of this protein.