Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation.
Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation.
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DOI：
10.7554/elife.39887
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发表时间：
2018-10-15
期刊：
影响因子：
7.7
通讯作者：
Bougdour A
中科院分区：
文献类型：
--
作者：
He H;Brenier-Pinchart MP;Braun L;Kraut A;Touquet B;Couté Y;Tardieux I;Hakimi MA;Bougdour A
细胞内寄生虫刚地弓形虫通过将效应蛋白递送到宿主细胞中以及时的方式改变基因表达来劫持进化上保守的宿主过程。我们鉴定了一种寄生虫致密颗粒蛋白GRA 18，其一旦在宿主细胞质中释放，就与β-连环蛋白破坏复合物的调节元件形成多功能复合物。通过与GSK 3/PP 2A-B56相互作用，GRA 18驱动β-catenin的上调以及对宿主细胞基因表达的下游效应。在巨噬细胞感染的情况下，GRA 18诱导通常与抗炎反应相关的特定基因组的表达，包括编码趋化因子CCL 17和CCL 22的基因。总的来说，这项研究增加了另一个原始的策略，T。弓形虫速殖子通过GSK 3/β-catenin轴重组宿主细胞相互作用组以选择性地重编程免疫基因表达。
The intracellular parasite Toxoplasma gondii, hijacks evolutionarily conserved host processes by delivering effector proteins into the host cell that shift gene expression in a timely fashion. We identified a parasite dense granule protein as GRA18 that once released in the host cell cytoplasm forms versatile complexes with regulatory elements of the β-catenin destruction complex. By interacting with GSK3/PP2A-B56, GRA18 drives β-catenin up-regulation and the downstream effects on host cell gene expression. In the context of macrophages infection, GRA18 induces the expression of a specific set of genes commonly associated with an anti-inflammatory response that includes those encoding chemokines CCL17 and CCL22. Overall, this study adds another original strategy by which T. gondii tachyzoites reshuffle the host cell interactome through a GSK3/β-catenin axis to selectively reprogram immune gene expression.