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

• Published in: eLife Vol. 7
• Main Authors: He, Huan, Brenier-Pinchart, Marie-Pierre, Braun, Laurence, Kraut, Alexandra, Touquet, Bastien, Coute, Yohann, Tardieux, Isabelle, Hakimi, Mohamed-Ali, Bougdour, Alexandre
• Format: Journal Article
• Language: English
• Published: eLife Sciences Publication 15.10.2018
• Subjects: Biochemistry; Biochemistry, Molecular Biology; Genomics; Immunology; Innate immunity; Life Sciences; Microbiology and Parasitology; Parasitology; Structural Biology; effector proteins; mouse; host-pathogen interactions; Toxoplasma gondii; toxoplasmosis; infectious disease; microbiology; human; parasitology
• ISSN: 2050-084X
• DOI: 10.7554/eLife.39887

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.