Toxoplasma Gondii Co-opts the Unfolded Protein Response To Enhance Migration and Dissemination of Infected Host Cells

is an intracellular parasite that reconfigures its host cell to promote pathogenesis. One consequence of parasitism is increased migratory activity of host cells, which facilitates dissemination. Here, we show that triggers the unfolded protein response (UPR) in host cells through calcium release from the endoplasmic reticulum (ER). We further identify a novel role for the host ER stress sensor protein IRE1 in pathogenesis. Upon infection, activates IRE1, engaging its noncanonical role in actin remodeling through the binding of filamin A. By inducing cytoskeletal remodeling via IRE1 oligomerization in host cells, enhances host cell migration and dissemination of the parasite to host organs Our study has identified novel mechanisms used by to induce dissemination of infected cells, providing new insights into strategies for treatment of toxoplasmosis. Cells that are infected with the parasite exhibit heightened migratory activity, which facilitates dissemination of the infection throughout the body. In this report, we identify a new mechanism used by to hijack its host cell and increase its mobility. We further show that the ability of to increase host cell migration involves not the enzymatic activity of IRE1 but rather IRE1 engagement with actin cytoskeletal remodeling. Depletion of IRE1 from infected host cells reduces their migration and significantly hinders dissemination of Our findings reveal a new mechanism underlying host-pathogen interactions, demonstrating how host cells are co-opted to spread a persistent infection around the body.