Pathogen-specific loss of host resistance in mice lackinq the lFN-y-inducible gene lGTP

摘要

Interferon-γ (IFN-vi is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. lGTP is the prototype for a family of lFN-opregulated 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 celI 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 gondi. By contrast, IFN-T receptor-deficient mice have increased susceptibil- ity to all three pathogens. Thus, IGTP defines an lFN-γ-regulated pathway with a specialized role in antimicrobial resistance.