Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Science. 2011 May 6;332(6030):717-21. doi: 10.1126/science.1201711.
Immune interferon gamma (IFN-γ) is essential for mammalian host defense against intracellular pathogens. IFN-γ induces nearly 2000 host genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-γ-inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, and Gbp10--conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps solicited host defense proteins, including the phagocyte oxidase, antimicrobial peptides, and autophagy effectors, to kill intracellular bacteria. Thus, specific 65-kD Gbps coordinate a potent oxidative and vesicular trafficking program to protect the host from infection.
免疫干扰素 γ（IFN-γ）对于哺乳动物宿主抵抗细胞内病原体至关重要。IFN-γ 诱导近 2000 个宿主基因，但很少有任何指定的功能。在这里，我们检查了一个完整的小鼠 65 千道尔顿（kD）鸟苷酸结合蛋白（Gbp）基因家族，作为小鼠和人类基因组中 43 个成员 IFN-γ诱导鸟苷三磷酸酶（GTPase）超家族的一部分。全家族功能丧失分析发现，至少有四种 Gbps——Gbp1、Gbp6、Gbp7 和 Gbp10——在巨噬细胞和基因缺陷动物中赋予了李斯特菌或分枝杆菌感染的细胞自主免疫。这些 Gbps 募集了宿主防御蛋白，包括吞噬细胞氧化酶、抗菌肽和自噬效应物，以杀死细胞内细菌。因此，特定的 65-kD Gbps 协调了一种有效的氧化和囊泡运输程序，以保护宿主免受感染。
