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

Science, 6 May 2011
Vol. 332, Issue 6030, p. 717-721
DOI: 10.1126/science.1201711

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

  1. Bae-Hoon Kim1,
  2. Avinash R. Shenoy1,
  3. Pradeep Kumar1,
  4. Rituparna Das1,2,
  5. Sangeeta Tiwari1,
  6. John D. MacMicking1,*
  1. 1Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
  2. 2Department of Internal Medicine, Division of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.
  1. *To whom correspondence should be addressed. E-mail: john.macmicking{at}


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.

  • Received for publication 14 December 2010.
  • Accepted for publication 29 March 2011.


B.-H. Kim, A. R. Shenoy, P. Kumar, R. Das, S. Tiwari, and J. D. MacMicking, A Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection. Science 332, 717-721 (2011).

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