# The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2

## TL;DR

The Toxoplasma protein TgWIP helps infected immune cells move faster by activating host enzymes Shp1 and Shp2, aiding parasite spread.

## Contribution

This study identifies how TgWIP interacts with Shp1 and Shp2 to alter dendritic cell motility during Toxoplasma infection.

## Key findings

- TgWIP contains SH2-binding motifs that activate Shp1 and Shp2 phosphatases in infected dendritic cells.
- TgWIP-induced hypermigration of dendritic cells is mediated through Rho-associated kinase (Rock).
- Mutant TgWIP lacking SH2-binding motifs fails to induce cell motility changes in dendritic cells.

## Abstract

The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of Toxoplasma relies on its swift dissemination to the central nervous system through a ‘Trojan Horse’ mechanism using infected leukocytes as carriers. Previous work found TgWIP, a protein secreted from Toxoplasma, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with Toxoplasma exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with Toxoplasma expressing a mutant TgWIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a TgWIP-Shp1/2 dependent manner. Collectively, the data uncover a molecular mechanism by which TgWIP modulates the migration dynamics of infected DCs in vitro.