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

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...

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Bibliographic Details
Main Authors: Huan He, Marie-Pierre Brenier-Pinchart, Laurence Braun, Alexandra Kraut, Bastien Touquet, Yohann Couté, Isabelle Tardieux, Mohamed-Ali Hakimi, Alexandre Bougdour
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-10-01
Series:eLife
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Online Access:https://elifesciences.org/articles/39887
Description
Summary: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.
ISSN:2050-084X