缺乏干扰素γ诱导基因IGTP的小鼠中宿主抗性的病原体特异性丧失。
Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.
作者信息
Taylor G A, Collazo C M, Yap G S, Nguyen K, Gregorio T A, Taylor L S, Eagleson B, Secrest L, Southon E A, Reid S W, Tessarollo L, Bray M, McVicar D W, Komschlies K L, Young H A, Biron C A, Sher A, Vande Woude G F
机构信息
Advanced BioScience Laboratories Basic Research Program, National Cancer Institute/Frederick Cancer Research and Development Center (NCI/FCRDC), Frederick, MD 21702, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):751-5. doi: 10.1073/pnas.97.2.751.
Abstract
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.
摘要
干扰素-γ（IFN-γ）对于抵御病原体至关重要，但其介导抗菌反应的分子在很大程度上尚不清楚。IGTP是一类IFN-γ调节基因家族的原型，这些基因编码定位于内质网的48 kDa GTP结合蛋白。我们培育出了IGTP缺陷小鼠，发现尽管这些小鼠的免疫细胞发育正常，对单核细胞增生李斯特菌和巨细胞病毒感染的清除也正常，但它们对原生动物寄生虫弓形虫的急性感染却表现出宿主抵抗力的严重丧失。相比之下，IFN-γ受体缺陷小鼠对这三种病原体的易感性均增加。因此，IGTP定义了一条在抗菌抗性中具有特殊作用的IFN-γ调节途径。
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