First Author | Kim BH | Year | 2011 |
Journal | Science | Volume | 332 |
Issue | 6030 | Pages | 717-21 |
PubMed ID | 21551061 | Mgi Jnum | J:172364 |
Mgi Id | MGI:5007562 | Doi | 10.1126/science.1201711 |
Citation | Kim BH, et al. (2011) A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial infection. Science 332(6030):717-21 |
abstractText | 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. |