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. 2011 May 6;332(6030):717-21.
doi: 10.1126/science.1201711.

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

Bae-Hoon Kim  1 , Avinash R Shenoy, Pradeep Kumar, Rituparna Das, Sangeeta Tiwari, John D MacMicking
Affiliations

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

Bae-Hoon Kim et al. Science. .

Abstract

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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