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Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence
Cellular Microbiology ( IF 3.4 ) Pub Date : 2020-10-11 , DOI: 10.1111/cmi.13278
Mary Akinyi Nyonda 1 , Pierre-Mehdi Hammoudi 1 , Shu Ye 1 , Jessica Maire 1 , Jean-Baptiste Marq 1 , Masahiro Yamamoto 2 , Dominique Soldati-Favre 1
Affiliation  

Toxoplasma gondii infects virtually any nucleated cell and resides inside a non‐phagocytic vacuole surrounded by a parasitophorous vacuolar membrane (PVM). Pivotal to the restriction of T. gondii dissemination upon infection in murine cells is the recruitment of immunity regulated GTPases (IRGs) and guanylate binding proteins (GBPs) to the PVM that leads to pathogen elimination. The virulent T. gondii type I RH strain secretes a handful of effectors including the dense granule protein GRA7, the serine–threonine kinases ROP17 and ROP18, and a pseudo‐kinase ROP5, that synergistically inhibit the recruitment of IRGs to the PVM. Here, we characterise GRA60, a novel dense granule effector, which localises to the vacuolar space and PVM and contributes to virulence of RH in mice, suggesting a role in the subversion of host cell defence mechanisms. Members of the host cell IRG defence system Irgb10 and Irga6 are recruited to the PVM of RH parasites lacking GRA60 as observed previously for the avirulent RHΔrop5 mutant, with RH preventing such recruitment. Deletion of GRA60 in RHΔrop5 leads to a recruitment of IRGs comparable to the single knockouts. GRA60 therefore represents a novel parasite effector conferring resistance to IRGs in type I parasites, and found associated to ROP18, a member of the virulence complex.

中文翻译:

弓形虫 GRA60 是一种效应蛋白,可调节宿主细胞自主免疫并有助于毒力

弓形虫几乎感染任何有核细胞,并存在于被寄生液泡膜 (PVM) 包围的非吞噬液泡内。限制弓形虫在鼠细胞感染后传播的关键是将免疫调节的 GTP 酶 (IRG) 和鸟苷酸结合蛋白 (GBP) 募集到 PVM,从而消除病原体。有毒的刚地弓形虫I 型 RH 菌株分泌少量效应物,包括致密颗粒蛋白 GRA7、丝氨酸-苏氨酸激酶 ROP17 和 ROP18 以及假激酶 ROP5,它们协同抑制 IRG 向 PVM 的募集。在这里,我们表征了 GRA60,一种新型致密颗粒效应器,它定位于液泡空间和 PVM,有助于小鼠 RH 的毒力,表明在颠覆宿主细胞防御机制中发挥作用。宿主细胞 IRG 防御系统 Irgb10 和 Irga6 的成员被招募到缺乏GRA60的 RH 寄生虫的 PVM,如之前对无毒 RHΔ rop5突变体所观察到的那样,RH 阻止了这种招募。缺失GRA60在RHΔ rop5导致与单次敲除相当的 IRGs 的招募。因此,GRA60 代表了一种新的寄生虫效应物,可赋予 I 型寄生虫对 IRG 的抗性,并发现与 ROP18(毒力复合物的成员)相关。
更新日期:2020-10-11
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