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

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

Research output: Contribution to journalArticle

274 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)717-721
Number of pages5
JournalScience
Volume332
Issue number6030
DOIs
StatePublished - May 6 2011

ASJC Scopus subject areas

  • General

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    Kim, B. H., Shenoy, A. R., Kumar, P., Das, R., Tiwari, S., & MacMicking, J. D. (2011). A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection. Science, 332(6030), 717-721. https://doi.org/10.1126/science.1201711