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Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation

Huan He 1 Marie-Pierre Brenier-Pinchart 1 Laurence Braun 1 Alexandra Kraut 2 Bastien Touquet 3 Yohann Coute 2 Isabelle Tardieux 3 Mohamed-Ali Hakimi 1, * Alexandre Bougdour 1, *
* Corresponding author
1 IAB - U1209 Inserm - UMR5309 CNRS - UGA - Team Host-pathogen interactions & immunity to infection
IAB [2016-2019] - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [2016-2019]
3 IAB - U1209 Inserm - UMR5309 CNRS - UGA - Team Membrane and Cell Dynamics of Host Parasite Interactions
IAB [2016-2019] - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [2016-2019]
Abstract : 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.
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https://www.hal.inserm.fr/inserm-02440386
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Huan He, Marie-Pierre Brenier-Pinchart, Laurence Braun, Alexandra Kraut, Bastien Touquet, et al.. Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation. eLife, eLife Sciences Publication, 2018, 7, pp.e39887. ⟨10.7554/eLife.39887⟩. ⟨inserm-02440386⟩

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