Characterization of a Toxoplasma effector uncovers an alternative GSK3/?-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 ?-catenin destruction complex. By interacting with GSK3/PP2A-B56, GRA18 drives ?-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/?-catenin axis to selectively reprogram immune gene expression.

SUBMITTER: He H 

PROVIDER: S-EPMC6214654 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature