title: A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection.
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.
authors.affiliation: Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Bae-Hoon
authors.initials: BH
authors.lastname: Kim
authors.forename: Avinash R
authors.initials: AR
authors.lastname: Shenoy
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Rituparna
authors.initials: R
authors.lastname: Das
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Tiwari
authors.forename: John D
authors.initials: JD
authors.lastname: MacMicking
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D034622:RNA Interference; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: C490288:Gbp2b protein, mouse; D010455:Peptides; D007371:Interferon-gamma; D019255:NADPH Oxidases; D019204:GTP-Binding Proteins; C526194:Gbp6 protein, mouse