PR001465 (Project)

Description:Despite a wealth of information about the mechanisms underlying immunity to disease following Leishmania infection, the correlates of protection in human leishmaniasis remain poorly defined. In that sense, a complete understanding of Leishmania biology and host-pathogen interactions is mandatory to fully recognize the molecular and cellular foundations of leishmaniasis pathogenesis. Recent studies have been demonstrating how innate cell metabolism associates to the development of resistance towards infection. As the causality in the immunometabolic connections remains untested, we propose to employ an integrative approach aiming at mapping the Leishmania-induced shifts in metabolic networks in macrophages and neutrophils, deciphering the molecular mechanisms of the metabolic shifts and establishing its causal relationship with the anti-leishmanial immune response mediated by these two types of cells. Dissecting these aspects is critical not only for an in-depth understanding of the biological mechanisms underlying Leishmania pathogenesis, but also to drive significant advances in the development of novel diagnostic and immunotherapeutic approaches.