Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it.
Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it.
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DOI：
10.1371/journal.pone.0024434
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Frickel EM
中科院分区：
文献类型：
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作者：
Virreira Winter S;Niedelman W;Jensen KD;Rosowski EE;Julien L;Spooner E;Caradonna K;Burleigh BA;Saeij JP;Ploegh HL;Frickel EM
IFN-γ是介导对细胞内寄生虫刚地弓形虫的抗性的主要细胞因子。p65鸟苷结合蛋白（GBPs）被IFN-γ强烈诱导。我们研究了小鼠GBP1 （mGBP1）在体外感染弓形虫后的行为，并证实了IFN-γ依赖性mGBP1在寄生液泡（PV）上的重新定位与弓形虫的毒力类型相关。我们确定了三种寄生因子，ROP16， ROP18和GRA15，它们决定了PV上mGBP1的菌株特异性积累。这些高度多态的蛋白质在很大程度上造成了菌株特异性的毒力差异。因此，我们的数据表明，弓形虫在动物中的毒力可能部分依赖于GBPs的识别。然而，含有克氏锥虫的吞噬体或空泡不招募mGBP1。共免疫沉淀显示mGBP2、mGBP4和mGBP5是mGBP1的结合伙伴。事实上，在弓形虫感染的细胞中，mGBP2和mGBP5与mGBP1共定位。因此，弓形虫在涉及GBPs的小鼠中引起细胞自主免疫反应。三种寄生毒力因子和未知的IFN-γ依赖性宿主因子调控着这一复杂的过程。根据所涉及菌株的毒力，许多GBPs作为大型多聚体结构的一部分被带到PV中以对抗弓形虫。
IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii.
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基于硅，体外和体内研究的鼠同源物簇的分析。
影响因子：
4.4
作者：
Kresse, Alexandra;Konermann, Carolin;Degrandi, Daniel;Beuter-Gunia, Cornelia;Wuerthner, Jan;Pfeffer, Klaus;Beer, Sandra
通讯作者：
Beer, Sandra
影响因子：
6.7
作者：
Martens S;Parvanova I;Zerrahn J;Griffiths G;Schell G;Reichmann G;Howard JC
通讯作者：
Howard JC
影响因子：
3.4
作者：
Khaminets A;Hunn JP;Könen-Waisman S;Zhao YO;Preukschat D;Coers J;Boyle JP;Ong YC;Boothroyd JC;Reichmann G;Howard JC
通讯作者：
Howard JC
影响因子：
4.4
作者：
Minns, Laurie A.;Menard, Laurence C.;Kasper, Lloyd H.
通讯作者：
Kasper, Lloyd H.
影响因子：
30.5
作者：
通讯作者：
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