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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Cell Line
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Immunity, Innate
  • Interferon-gamma / immunology*
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / immunology
  • Listeria monocytogenes / pathogenicity
  • Listeriosis / immunology*
  • Listeriosis / metabolism
  • Listeriosis / microbiology
  • Lysosomes / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Mice
  • Mycobacterium bovis / growth & development
  • Mycobacterium bovis / immunology
  • Mycobacterium bovis / pathogenicity
  • NADPH Oxidases / metabolism
  • Oxidation-Reduction
  • Peptides / metabolism
  • Phagocytosis
  • Phagosomes / metabolism
  • RNA Interference
  • Tuberculosis / immunology*
  • Tuberculosis / metabolism
  • Tuberculosis / microbiology

Substances

  • Gbp2b protein, mouse
  • Peptides
  • Interferon-gamma
  • NADPH Oxidases
  • GTP-Binding Proteins
  • Gbp6 protein, mouse