生物
先天免疫系统
毒力
微生物学
病菌
细胞内寄生虫
弓形虫
免疫系统
干扰素
个人识别码1
病毒学
细胞生物学
免疫学
磷酸化
抗体
丝氨酸
生物化学
基因
作者
Daniel Fisch,Moritz M. Pfleiderer,Eleni Anastasakou,Gillian M Mackie,Fabian Wendt,Xiangyang Li,Barbara Clough,Samuel Lara-Reyna,Vesela Encheva,Ambrosius P. Snijders,Hironori Bando,Masahiro Yamamoto,Andrew D Beggs,Jason Mercer,Avinash R. Shenoy,Bernd Wollscheid,Kendle M. Maslowski,Wojciech P. Galej,Eva‐Maria Frickel
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2023-10-06
卷期号:382 (6666)
被引量:5
标识
DOI:10.1126/science.adg2253
摘要
Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)–inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense by attacking intracellular pathogens and by inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression in the absence of IFN-γ killed the cells and induced Golgi fragmentation. IFN-γ exposure improved macrophage survival through the activity of the kinase PIM1. PIM1 phosphorylated GBP1, leading to its sequestration by 14-3-3σ, which thereby prevented GBP1 membrane association. During Toxoplasma gondii infection, the virulence protein TgIST interfered with IFN-γ signaling and depleted PIM1, thereby increasing GBP1 activity. Although infected cells can restrain pathogens in a GBP1-dependent manner, this mechanism can protect uninfected bystander cells. Thus, PIM1 can provide a bait for pathogen virulence factors, guarding the integrity of IFN-γ signaling.
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