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Science 332 (6030): 717-721

Copyright © 2011 by the American Association for the Advancement of Science

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

Bae-Hoon Kim,1 Avinash R. Shenoy,1 Pradeep Kumar,1 Rituparna Das,1,2 Sangeeta Tiwari,1 John D. MacMicking1,*

Abstract: 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.

1 Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
2 Department of Internal Medicine, Division of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.

* To whom correspondence should be addressed. E-mail: john.macmicking{at}yale.edu

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