TY - JOUR
T1 - A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection
AU - Kim, Bae Hoon
AU - Shenoy, Avinash R.
AU - Kumar, Pradeep
AU - Das, Rituparna
AU - Tiwari, Sangeeta
AU - MacMicking, John D.
PY - 2011/5/6
Y1 - 2011/5/6
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1201711
DO - 10.1126/science.1201711
M3 - Article
C2 - 21551061
AN - SCOPUS:79955777383
SN - 0036-8075
VL - 332
SP - 717
EP - 721
JO - Science
JF - Science
IS - 6030
ER -