Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication
Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication
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DOI：
10.1073/pnas.1205635110
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发表时间：
2013-01-02
影响因子：
11.1
通讯作者：
Pfeffer, Klaus
中科院分区：
文献类型：
--
作者：
Degrandi, Daniel;Kravets, Elisabeth;Pfeffer, Klaus
干扰素-γ协调宿主对细胞内病原体的反应。鸟苷结合蛋白(GBP)是干扰素-γ诱导的转录反应中含量最丰富的成员。MGBPs是一种GTP酶，可被干扰素-γ、其他促炎细胞因子、Toll样受体激动剂以及单核细胞增生性李斯特菌和弓形虫感染所特异性上调。MGBP2定位于弓形虫的寄生空泡(Pv)，但其分子功能及其结构域在弓形虫感染中的作用尚不清楚。在这里，我们发现mGBP2在几种细胞类型中都有高表达，包括刺激后的T细胞和B细胞。我们提供的证据表明，C-末端结构域对于弓形虫PV的招募是充分和必要的。在功能上，mGBP2抑制了弓形虫的增殖，因为mGBP2缺陷的细胞在弓形虫的复制控制上存在缺陷。最终，mGBP2缺陷小鼠对弓形虫具有明显的免疫易感性。综上所述，mGBP2是介导抗寄生虫抗性的重要免疫效应分子。
IFN-gamma orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-gamma-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-gamma, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the C-terminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.