Pathogen-specific loss of host resistance in mice lacking the IFN-γ-inducible gene IGTP

Interferon-γ (IFN-γ) is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. IGTP is the prototype for a family of IFN-γ-regulated genes that encode 48-kDa GTP-binding proteins that localize to the endoplasmic reticulum. We have gene...

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Main Authors: Taylor, Gregory A., Collazo, Carmen M., Yap, George S., Nguyen, Khuong, Gregorio, Theresa A., Taylor, Lynn S., Eagleson, Bryn, Secrest, Lisa, Southon, Eileen A., Reid, Susan W., Tessarollo, Lino, Bray, Mike, McVicar, Dan W., Komschlies, Kristin L., Young, Howard A., Biron, Christine A., Sher, Alan, Vande Woude, George F.
Formato: Artigo
Idioma:en
Publicado em: The National Academy of Sciences 2000
Assuntos:
Biological Sciences
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC15402/
https://ncbi.nlm.nih.gov/pubmed/10639151
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Descrição
Resumo:Interferon-γ (IFN-γ) is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. IGTP is the prototype for a family of IFN-γ-regulated genes that encode 48-kDa GTP-binding proteins that localize to the endoplasmic reticulum. We have generated IGTP-deficient mice and found that, despite normal immune cell development and normal clearance of Listeria monocytogenes and cytomegalovirus infections, the mice displayed a profound loss of host resistance to acute infections of the protozoan parasite Toxoplasma gondii. By contrast, IFN-γ receptor-deficient mice have increased susceptibility to all three pathogens. Thus, IGTP defines an IFN-γ-regulated pathway with a specialized role in antimicrobial resistance.

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