Elucidation of novel innate immune system by analysis of host-parasite interaction

干扰素-g是宿主抵御细胞内病原体的必需物质。干扰素-g刺激天然免疫细胞可上调免疫相关GTP酶等2000个效应基因的表达，其中包括P65鸟苷结合蛋白(GBP)家族基因。我们发现，针对细胞内寄生虫弓形虫的宿主细胞免疫需要一簇GBP基因。我们通过定向染色体工程产生了定位于3号染色体上的所有6个GBP基因缺失的小鼠。缺乏Gbpchr3的小鼠对弓形虫感染高度敏感，导致免疫器官中寄生虫负担增加。此外，Gbpchr3缺失的巨噬细胞在干扰素-g介导的抑制弓形虫细胞内生长方面存在缺陷。此外，Gbpchr3的一些成员在Gbpchr3缺失的细胞中恢复了对弓形虫的保护反应。因此，Gbpchr3在抗T.控制干扰素-g介导的细胞先天免疫的弓形虫宿主防御。

Interferon-g (IFN-g) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-g up-regulates ~2000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (GBP) family genes. We show that a cluster of GBP genes is required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six GBP genes located on chromosome 3 by targeted chromosome engineering. Mice lacking Gbpchr3 were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbpchr3-deleted macrophages were defective in IFN-g-mediated suppression of T. gondii intracellular growth. In addition, some members of Gbpchr3 restored the protective response against T. gondii in Gbpchr3-deleted cells. Thus, Gbpchr3 redundantly play a pivotal role in anti-T. gondii host defense by controlling IFN-g-mediated cellular innate immunity.