Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.
Interferon-gamma (IFN-gamma) 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-gamma-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-gamma receptor-deficient mice have increased susceptibility to all three pathogens. Thus, IGTP defines an IFN-gamma-regulated pathway with a specialized role in antimicrobial resistance.
Taylor, GA; Collazo, CM; Yap, GS; Nguyen, K; Gregorio, TA; Taylor, LS; Eagleson, B; Secrest, L; Southon, EA; Reid, SW; Tessarollo, L; Bray, M; McVicar, DW; Komschlies, KL; Young, HA; Biron, CA; Sher, A; Vande Woude, GF
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