Rivera-Cuevas Yolanda, Clough Barbara, Frickel Eva-Maria
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston B15 2TT, United Kingdom.
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston B15 2TT, United Kingdom.
Curr Opin Immunol. 2023 Oct;84:102373. doi: 10.1016/j.coi.2023.102373. Epub 2023 Aug 1.
Cell-intrinsic defense is an essential part of the immune response against intracellular pathogens regulated by cytokine-induced proteins and pathways. One of the most upregulated families of proteins in this defense system are the guanylate-binding proteins (GBPs), large GTPases of the dynamin family, induced in response to interferon gamma. Human GBPs (hGBPs) exert their antimicrobial activity through detection of pathogen-associated molecular patterns and/or damage-associated molecular patterns to execute control mechanisms directed at the pathogen itself as well as the vacuolar compartments in which it resides. Consequently, hGBPs are also inducers of canonical and noncanonical inflammasome responses leading to host cell death. The mechanisms are both cell-type and pathogen-dependent with hGBP1 acting as a pioneer sensor for intracellular invaders. This review focuses on the most recent functional roles of hGBPs in pathways of pathogen detection, destruction, and host cell death induction.
细胞内在防御是针对细胞内病原体的免疫反应的重要组成部分，受细胞因子诱导的蛋白质和信号通路调控。在这种防御系统中，最上调的蛋白质家族之一是鸟苷酸结合蛋白（GBPs），它是发动蛋白家族的大型GTP酶，在干扰素γ的作用下被诱导产生。人类GBPs（hGBPs）通过检测病原体相关分子模式和/或损伤相关分子模式来发挥其抗菌活性，从而执行针对病原体本身及其所驻留的液泡区室的控制机制。因此，hGBPs也是导致宿主细胞死亡的经典和非经典炎性小体反应的诱导剂。这些机制既依赖于细胞类型，也依赖于病原体，其中hGBP1作为细胞内入侵者的先驱传感器。本综述重点关注hGBPs在病原体检测、破坏和宿主细胞死亡诱导途径中的最新功能作用。
