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Publication : A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection.

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.
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