Cross-talk between lipid metabolism, stress response and Toxoplasma gondii infection in dendritic cells.

Toxoplasmosis is a disease caused by the apicomplexan parasite Toxoplasma gondii. Although, the parasite is well controlled in immunocompetent people, toxoplasmosis is still a major issue for pregnant women and immunodeficient individuals. Thus, it is important to understand how T. gondii interacts with the immune system. The control of T. gondii relies on cell-autonomous immunity and the establishment of a Th1 response. Here, we aim at understanding how infection of dendritic cells (DCs) impacts their activation, metabolism, and ability to trigger adaptive immune responses. Indeed, DCs are key players in the detection of invading pathogens, and activation of specific T cells through antigen presentation. Importantly, immune signalling tightly interacts with metabolic pathways, which are known to be modulated by intracellular pathogens like T. gondii. We previously showed that the Unfolded Protein Response (UPR), a key sensor of lipid metabolic and oxidative stresses, is critical for pro-inflammatory cytokine production and parasite-derived MHC-I antigen presentation in infected Bone-Marrow derived DCs. In this project, using transcriptomic and lipidomic analysis, we evaluate the differential modulation of immune and metabolic pathways in type I versus type II parasite infected DCs. We aim at elucidating how these changes may impact on parasite vacuole membrane integrity and MHC-I antigen presentation. We also investigate the role of the IRE1 pathway of the UPR in these processes. On a larger scale, our study aims to shed light on the pivotal role of the UPR response and lipid metabolism in the regulation of cellular defenses triggered against intracellular pathogens.