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

干扰素-g （IFN-g）对宿主防御细胞内病原体至关重要。IFN-g对先天免疫细胞的刺激上调了约2000个效应基因，如免疫相关的gtpase，包括p65鸟苷酸结合蛋白（GBP）家族基因。我们表明，一簇GBP基因是宿主细胞免疫细胞内寄生虫弓形虫所必需的。通过定向染色体工程，我们培育出了3号染色体上所有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，导致免疫器官寄生虫负担增加。此外，缺失gbpchr3的巨噬细胞在ifn -g介导的弓形虫细胞内生长抑制中存在缺陷。此外，一些Gbpchr3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冗余地在抗t中起关键作用。通过控制ifn -g介导的细胞先天免疫来防御弓形虫宿主。

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.