Toxoplasma gondii exploits the host Wnt/β-catenin pathway to successfully establish intracellular infection

Speaker

Cameron Ranken

CETI & UNM Biology

When: Apr 26, 2019 - 12:00pm - 01:00pm

Where: 258 Castetter Hall

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, we obtained data indicating that direct contact between parasites and cells is required for increased β-catenin expression. To examine the functional consequences of augmented β-catenin levels, we determined the effect of a panel of Wnt/β-catenin inhibitors on the ability of T. gondii to successfully establish infection. Using both dendritic cells and fibroblasts, we found up to 80% inhibition of infection in the presence of the small molecule inhibitors. Most recent efforts have been directed towards determining whether host β-catenin is required for the invasion event itself, or whether its role is in maintenance of the parasitophorous vacuole in newly invaded cells.