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.
- Alexandre Bougdour
- Laurence Braun
- Mohamed-ali Hakimi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed under pathogen-free conditions in accordance with established institutional guidance and approved protocols from the institutional animal care and use committee protocol (#175_UHTA-UMR5163-AB-01) of the University Grenoble Alpes. For all the experiments performed, every effort was made to minimize suffering.
- Dominique Soldati-Favre, University of Geneva, Switzerland
© 2018, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.