Innate immune cells tightly coordinate their metabolic programs to support a proper immunological function. As such, perturbed metabolic fluxes imply decisive effects on immune cell activation eventuating in their ability to control a pathogen and the disease inflicted by it. This project is based on the hypothesis that the metabolic crosstalk between a pathogen and their host is crucial to define microbial evasion and host protective strategies. Focusing on the protozoan Leishmania spp., responsible for chronic infections leading to elevated numbers of morbidity and mortality, this project aims to: i) elucidate the immunometabolic networks regulating the innate immune anti-leishmanial response that plays a crucial role in defining susceptibility to infection; ii) investigate how lipid enrichment and adipose tissue accumulation impact parasite proliferation and reservoir, redefining ultimately the host immune landscape, and iii) decipher the metabolic-epigenetic interface in infected macrophages. Understanding the intricate mechanistic level of connection between metabolism, epigenetic and immune effector functions will boost the design of new immunotherapeutic agents.