Publication Date:
2011-05-10
Description:
Immune interferon gamma (IFN-gamma) is essential for mammalian host defense against intracellular pathogens. IFN-gamma 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-gamma-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Bae-Hoon -- Shenoy, Avinash R -- Kumar, Pradeep -- Das, Rituparna -- Tiwari, Sangeeta -- MacMicking, John D -- R01 AI068041-01A1/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2011 May 6;332(6030):717-21. doi: 10.1126/science.1201711.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Microbial Pathogenesis, Boyer Centre for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21551061" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Autophagy
;
Cell Line
;
GTP-Binding Proteins/chemistry/genetics/*metabolism
;
Humans
;
Immunity, Innate
;
Interferon-gamma/*immunology
;
Listeria monocytogenes/growth & development/immunology/pathogenicity
;
Listeriosis/*immunology/metabolism/microbiology
;
Lysosomes/metabolism
;
Macrophages/*immunology/metabolism/*microbiology
;
Mice
;
Mycobacterium bovis/growth & development/immunology/pathogenicity
;
NADPH Oxidase/metabolism
;
Oxidation-Reduction
;
Peptides/metabolism
;
Phagocytosis
;
Phagosomes/metabolism
;
RNA Interference
;
Tuberculosis/*immunology/metabolism/microbiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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