ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

文献类型： 外文期刊

第一作者： Hao, Yu

作者： Hao, Yu;Yang, Bo;Yang, Jinke;Shi, Xijuan;Yang, Xing;Zhang, Dajun;Zhao, Dengshuai;Yan, Wenqian;Chen, Lingling;Zheng, Haixue;Zhang, Keshan;Liu, Xiangtao

作者机构：

关键词： ZBP1; innate immunity; apoptosis; pyroptosis; necroptosis; auto-inflammatory diseases; tumor immunity; signaling transduction; pathogen-host interactions

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：6.208； 五年影响因子：6.628 ）

ISSN：

年卷期： 2022 年 23 卷 18 期

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收录情况： SCI

摘要： Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in innate immune response and the multiple inflammatory cell death known as PANoptosis. The initiation of ZBP1 signaling requires recognition of left-handed double-helix Z-nucleic acid (includes Z-DNA and Z-RNA) and subsequent signaling transduction depends on the interaction between ZBP1 and its adapter proteins, such as TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3. ZBP1 activated innate immunity, including type-I interferon (IFN-I) response and NF-kappa B signaling, constitutes an important line of defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is a double-edged sword in anti-infection, auto-inflammatory diseases, and tumor immunity. ZBP1-mediated PANoptosis is beneficial for eliminating infected cells and tumor cells, but abnormal or excessive PANoptosis can lead to a strong inflammatory response that is harmful to the host. Thus, pathogens and host have each developed multiplex tactics targeting ZBP1 signaling to maintain strong virulence or immune homeostasis. In this paper, we reviewed the mechanisms of ZBP1 signaling, the effects of ZBP1 signaling on host immunity and pathogen infection, and various antagonistic strategies of host and pathogen against ZBP1. We also discuss existent gaps regarding ZBP1 signaling and forecast potential directions for future research.

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