The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens.
The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens.
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DOI：
10.1007/s00335-010-9293-3
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发表时间：
2011-02
期刊：
影响因子：
2.5
通讯作者：
Howard, Jonathan C.
中科院分区：
文献类型：
--
作者：
Hunn, Julia P.;Feng, Carl G.;Sher, Alan;Howard, Jonathan C.
免疫相关 GTP 酶 (IRG) 属于大型干扰素诱导型 GTP 酶家族，构成细胞自主抵抗系统，对于控制小鼠体内弓形虫等液泡病原体至关重要。最近的结果表明，许多 IRG 成员在入侵弓形虫的寄生液泡中协同积累，导致液泡和寄生虫的破坏以及随后的宿主细胞坏死。不同 IRG 蛋白之间复杂的调控相互作用对于这些过程是必要的。这种精细平衡的系统受到干扰，例如，重要的负调节因子 Irgm1 或自噬调节因子 Atg5 的单一遗传缺陷，会导致效应 IRG 蛋白在 IFNγ 诱导下自发激活。这种激活具有细胞毒性后果，导致 Irgm1 缺陷小鼠出现严重的淋巴细胞减少、巨噬细胞缺陷和适应性免疫系统衰竭。然而，Irgm1 在吞噬体成熟和自噬诱导中具有替代功能。 IRG 系统主要在小鼠中进行研究，但 IRG 基因存在于整个哺乳动物谱系中。有趣的是，即使在密切相关的物种之间，基因的数量、类型和多样性也存在很大差异，这可能反映了由 IRG 抗性蛋白和病原体毒力因子之间的武装竞赛驱动的密切宿主-病原体共同进化。 IRG 蛋白是多态性弓形虫毒力因子的靶标，不同小鼠品系之间 IRG 系统的遗传变异与对毒力弓形虫菌株的耐药性和易感性相关。
The immunity-related GTPases (IRGs) belong to the family of large, interferon-inducible GTPases and constitute a cell-autonomous resistance system essential for the control of vacuolar pathogens like Toxoplasma gondii in mice. Recent results demonstrated that numerous IRG members accumulate collaboratively at the parasitophorous vacuole of invading T. gondii leading to the destruction of the vacuole and the parasite and subsequent necrotic host cell death. Complex regulatory interactions between different IRG proteins are necessary for these processes. Disturbance of this finely balanced system, e.g., by single genetic deficiency for the important negative regulator Irgm1 or the autophagic regulator Atg5, leads to spontaneous activation of the effector IRG proteins when induced by IFNγ. This activation has cytotoxic consequences resulting in a severe lymphopenia, macrophage defects, and failure of the adaptive immune system in Irgm1-deficient mice. However, alternative functions in phagosome maturation and induction of autophagy have been proposed for Irgm1. The IRG system has been studied primarily in mice, but IRG genes are present throughout the mammalian lineage. Interestingly, the number, type, and diversity of genes present differ greatly even between closely related species, probably reflecting intimate host-pathogen coevolution driven by an armed race between the IRG resistance proteins and pathogen virulence factors. IRG proteins are targets for polymorphic T. gondii virulence factors, and genetic variation in the IRG system between different mouse strains correlates with resistance and susceptibility to virulent T. gondii strains.
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免疫相关的GTPase IRGM1通过防止干扰素γ诱导的细胞死亡促进活化的CD4+ T细胞群体的扩张。
影响因子：
30.5
作者：
Feng, Carl G.;Zheng, Lixin;Jankovic, Dragana;Bafica, Andre;Cannons, Jennifer L.;Watford, Wendy T.;Chaussabel, Damien;Hieny, Sara;Caspar, Patricia;Schwartzberg, Pamela L.;Lenardo, Michael J.;Sher, Alan
通讯作者：
Sher, Alan
影响因子：
32.4
作者：
Bougneres, Laurence;Helft, Julie;Tiwari, Sangeeta;Vargas, Pablo;Chang, Benny Hung-Junn;Chan, Lawrence;Campisi, Laura;Lauvau, Gregoire;Hugues, Stephanie;Kumar, Pradeep;Kamphorst, Alice O.;Dumenil, Ana-Maria Lennon;Nussenzweig, Michel;MacMicking, John D.;Amigorena, Sebastian;Guermonprez, Pierre
通讯作者：
Guermonprez, Pierre
影响因子：
64.8
作者：
Gao, Song;von der Malsburg, Alexander;Daumke, Oliver
通讯作者：
Daumke, Oliver
影响因子：
64.8
作者：
Cadwell, Ken;Liu, John Y.;Brown, Sarah L.;Miyoshi, Hiroyuki;Loh, Joy;Lennerz, Jochen K.;Kishi, Chieko;Kc, Wumesh;Carrero, Javier A.;Hunt, Steven;Stone, Christian D.;Brunt, Elizabeth M.;Xavier, Ramnik J.;Sleckman, Barry P.;Li, Ellen;Mizushima, Noboru;Stappenbeck, Thaddeus S.;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.
影响因子：
4.4
作者：
Feng, CG;Collazo-Custodio, CM;Sher, A
通讯作者：
Sher, A