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

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
Contributor : Mohamed-Ali Hakimi <>
Submitted on : Wednesday, January 15, 2020 - 10:40:08 AM
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Huan He (eLIFE, 2018).pdf
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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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