Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
mBio. 2020 Jan 21;11(1):e02993-19. doi: 10.1128/mBio.02993-19.
Members of the murine guanylate-binding protein family (mGBP) are induced by interferon gamma (IFN-γ) and have been shown to be important factors in cell-autonomous immunity toward the intracellular pathogen Previously, we identified that mGBP2 mediates disruption of the parasitophorous vacuole membrane (PVM) and directly assaults the plasma membrane of the parasite. Here, we show that mGBP7-deficient mice are highly susceptible to infection. This is demonstrated by the loss of parasite replication control, pronounced development of ascites, and death of the animals in the acute infection phase. Interestingly, live-cell microscopy revealed that mGBP7 recruitment to the PVM occurs after mGBP2 recruitment, followed by disruption of the PVM and integrity and accumulation of mGBP7 inside the parasite. This study defines mGBP7 as a crucial effector protein in resistance to intracellular Guanylate-binding proteins (GBPs) are induced by the inflammatory cytokine interferon gamma (IFN-γ) and have been shown to be important factors in the defense of the intracellular pathogen In previous studies, we showed that members of the mouse GBP family, such as mGBP2 and mGBP7, accumulate at the parasitophorous vacuole of , which is the replicatory niche of the parasite. In this study, we show that mice deficient in mGBP7 succumb early after infection with , showing a complete failure of resistance to the pathogen. On a molecular level, mGBP7 is found directly at the parasite, likely mediating its destruction.
鼠源鸟苷酸结合蛋白家族（mGBP）成员受干扰素 γ（IFN-γ）诱导，已被证明是细胞自主免疫针对细胞内病原体的重要因素。此前，我们鉴定出 mGBP2 介导寄生泡膜（PVM）的破坏，并直接攻击寄生虫的质膜。在这里，我们表明 mGBP7 缺陷小鼠对 感染高度敏感。这表现在寄生虫复制控制的丧失、腹水的显著发展以及动物在急性感染阶段的死亡。有趣的是，活细胞显微镜显示 mGBP7 募集到 PVM 发生在 mGBP2 募集之后，随后 PVM 和 的完整性被破坏，mGBP7 在寄生虫内部积累。这项研究将 mGBP7 定义为抵抗细胞内 的关键效应蛋白。
鸟苷酸结合蛋白（GBPs）由炎症细胞因子干扰素 γ（IFN-γ）诱导，已被证明是防御细胞内病原体的重要因素。在之前的研究中，我们表明，鼠源 GBP 家族的成员，如 mGBP2 和 mGBP7，在 的寄生泡中积累，这是寄生虫的复制生态位。在这项研究中，我们表明 mGBP7 缺陷的小鼠在感染 后早期死亡，对病原体完全没有抵抗力。在分子水平上，mGBP7 直接位于寄生虫上，可能介导其破坏。
