A Family of IFN-gamma-Inducible 65-kD GTPases Protects Against Bacterial Infection

作者：Kim Bae Hoon; Shenoy Avinash R; Kumar Pradeep; Das Rituparna; Tiwari Sangeeta; MacMicking John D^*

来源：Science, 2011, 332(6030): 717-721.

DOI：10.1126/science.1201711

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.

• 出版日期2011-5-6