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.
Highlights
Toxoplasma gondii is the causative agent of toxoplasmosis, a widespread parasitic disease in humans which has been recognized as leading cause of deaths attributed to foodborne illness in the United States (Scallan et al, 2015)
GRA18 protein accommodates both a signal peptide for targeting to the secretory pathway and a canonical TEXEL motif found on Parasitophorous Vacuole (PV) residing proteins (i.e. GRAs proteins), some of which traffic across the PV Membrane (PVM) to reach the host cell cytoplasm (Coffey et al, 2015; Hakimi et al, 2017; Hammoudi et al, 2015; Hsiao et al, 2013) (Figure 1A)
In cells infected by type II tachyzoites (Pru ku80) expressing the chimeric GRA18-HF under the control of the promoter of GRA1, a similar GRA18-HF cytoplasmic distribution was observed (Figure 1C, lower panel) the chimeric construct significantly accumulated in the parasite cytoplasm and the PV space, suggesting that secretion and export are limiting steps for GRA18 trafficking
Summary
Toxoplasma gondii is the causative agent of toxoplasmosis, a widespread parasitic disease in humans which has been recognized as leading cause of deaths attributed to foodborne illness in the United States (Scallan et al, 2015). T. gondii belongs to the protozoan phylum Apicomplexa and as most Apicomplexa species, develops and proliferates inside a surrogate host cell. The invasive tachyzoite stage of T. gondii triggers the formation of a unique membrane-bound compartment called the Parasitophorous Vacuole (PV). Several studies have highlighted the contribution of parasite effectors delivered in the host cell at the very onset of-or post-invasion to promote folding and maturation of a functional PV (DelormeWalker et al, 2012; Hakimi et al, 2017). Effectors are released from two specialized sets of secretory organelles including the pear-shaped rhoptries that contain the ROP16 and ROP38 effectors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
