A Cluster of Interferon-gamma-Inducible p65 GTPases Plays a Critical Role in Host Defense against Toxoplasma gondii

作者：Yamamoto Masahiro^*; Okuyama Megumi; Ma Ji Su; Kimura Taishi; Kamiyama Naganori; Saiga Hiroyuki; Ohshima Jun; Sasai Miwa; Kayama Hisako; Okamoto Toru; Huang David C S; Soldati Favre Dominique; Horie Kyoji; Takeda Junji; Takeda Kiyoshi

来源：Immunity, 2012, 37(2): 302-313.

DOI：10.1016/j.immuni.2012.06.009

Interferon-gamma (IFN-gamma) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-gamma upregulates similar to 2,000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (Gbp) family genes. We show that a cluster of Gbp genes was required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six Gbp genes located on chromosome 3 (Gbp(chr3)) by targeted chromosome engineering. Mice lacking Gbp(chr3) were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbp(chr3)-deleted macrophages were defective in IFN-gamma-mediated suppression of T. gondii intracellular growth and recruitment of IFN-gamma-inducible p47 GTPase Irgb6 to the parasitophorous vacuole. In addition, some members of Gbp(chr3) restored the protective response against T. gondii in Gbp(chr3)-deleted cells. Our results suggest that Gbp(chr3) play a pivotal role in anti-T. gondii host defense by controlling IFN-gamma-mediated Irgb6-dependent cellular innate immunity.

• 出版日期2012-8-24
• 单位河北医科大学