Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation.
Huan HeMarie-Pierre Brenier-PinchartLaurence BraunAlexandra KrautBastien TouquetYohann CoutIsabelle TardieuxMohamed-Ali HakimiAlexandre BougdourPublished in: eLife (2018)
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.
Keyphrases
- gene expression
- toxoplasma gondii
- single cell
- epithelial mesenchymal transition
- inflammatory response
- cell therapy
- cell proliferation
- dna methylation
- signaling pathway
- transcription factor
- oxidative stress
- pi k akt
- poor prognosis
- mesenchymal stem cells
- dendritic cells
- toll like receptor
- lipopolysaccharide induced
- binding protein
- liver injury
- drug induced