Characterization of a <i>Toxoplasma</i> effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30320549.
- Also identified by DOI 10.7554/eLife.39887 and PMC identifier 6214654.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The intracellular parasite <i>Toxoplasma gondii,</i> 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 <i>T. gondii</i> tachyzoites reshuffle the host cell interactome through a GSK3/β-catenin axis to selectively reprogram immune gene expression.
Medical subject headings
- Glycogen Synthase Kinase 3
- Inflammation
- Signal Transduction
- Toxoplasma
- beta Catenin