细胞内寄生虫
GTP酶
细胞内
吞噬细胞
基因
微生物学
效应器
细胞生物学
鸟苷
基因家族
先天免疫系统
免疫
免疫系统
生物
基因组
遗传学
作者
Bae Hoon Kim,Avinash R. Shenoy,Pradeep Kumar,Rituparna Das,Sangeeta Tiwari,John D. MacMicking
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2011-05-06
卷期号:332 (6030): 717-721
被引量:418
标识
DOI:10.1126/science.1201711
摘要
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.
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