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Elife. 2018 Oct 15;7. pii: e39887. doi: 10.7554/eLife.39887.

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

Author information

1
Team Host-pathogen interactions & immunity to infection, University of Grenoble Alpes, Inserm, CNRS, IAB, Grenoble, France.
2
University of Grenoble Alpes, CEA, Inserm, BIG-BGE, Grenoble, France.
3
Team Membrane and Cell Dynamics of Host Parasite Interactions, University of Grenoble Alpes, Inserm, CNRS, IAB, Grenoble, France.

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.

KEYWORDS:

Toxoplasma gondii; effector proteins; host-pathogen interactions; human; infectious disease; microbiology; mouse; parasitology; toxoplasmosis

PMID:
30320549
PMCID:
PMC6214654
DOI:
10.7554/eLife.39887
[Indexed for MEDLINE]
Free PMC Article

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