Team Host-pathogen interactions & immunity to infection, University of Grenoble Alpes, Inserm, CNRS, IAB, Grenoble, France.
University of Grenoble Alpes, CEA, Inserm, BIG-BGE, Grenoble, France.
Elife. 2018 Oct 15;7:e39887. doi: 10.7554/eLife.39887.
The intracellular parasite 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 tachyzoites reshuffle the host cell interactome through a GSK3/β-catenin axis to selectively reprogram immune gene expression.
细胞内寄生虫通过将效应蛋白递送到宿主细胞中，从而劫持进化保守的宿主过程，及时改变基因表达。我们鉴定出一种寄生虫致密颗粒蛋白 GRA18，其一旦被释放到宿主细胞质中，就会与 β-连环蛋白降解复合物的调节元件形成多功能复合物。通过与 GSK3/PP2A-B56 相互作用，GRA18 驱动 β-连环蛋白的上调，并对宿主细胞基因表达产生下游影响。在巨噬细胞感染的情况下，GRA18 诱导一组与抗炎反应相关的特定基因的表达，包括编码趋化因子 CCL17 和 CCL22 的基因。总的来说，这项研究增加了另一种原始策略，即速殖子通过 GSK3/β-连环蛋白轴重新排列宿主细胞相互作用组，从而选择性地上调免疫基因表达。
