A Family of IFN-γ-Inducible 65-kD GTPases Protects Against Bacterial Infection
A Family of IFN-γ-Inducible 65-kD GTPases Protects Against Bacterial Infection
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DOI：
10.1126/science.1201711
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发表时间：
2011-05-06
期刊：
影响因子：
56.9
通讯作者：
MacMicking, John D.
中科院分区：
文献类型：
--
作者：
Kim, Bae-Hoon;Shenoy, Avinash R.;MacMicking, John D.
免疫干扰素-γ是哺乳动物抵抗细胞内病原体的必需免疫因子。干扰素-γ可诱导近2000个宿主基因，但很少有基因具有指定的功能。在这里，我们研究了一个完整的小鼠65kodalton(KD)鸟氨酸结合蛋白(GBP)基因家族，作为43个成员的干扰素-γ诱导的鸟苷三磷酸酶(GTPase)超家族的一部分，在小鼠和人类基因组中。全家庭功能丧失分析发现，至少有四个GBP-GBP1、GBP6、GBP7和GBP10-赋予了对巨噬细胞和基因缺陷动物中李斯特菌或分枝杆菌感染的细胞自主免疫。这些GBP请求宿主防御蛋白，包括吞噬细胞氧化酶、抗菌肽和自噬效应器，以杀死细胞内的细菌。因此，特定的65-kD Gbps协调一个强大的氧化和囊泡运输计划，以保护宿主免受感染。
Immune interferon gamma (IFN-gamma) is essential for mammalian host defense against intracellular pathogens. IFN-gamma 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-gamma-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.