PR003081 (Project)

Description:Visceral leishmaniasis (VL), caused by Leishmania infantum in Brazil, exhibits clinical features associated with alterations in the host lipid metabolism. Previous studies link hypertriglyceridemia, elevated VLDL levels, and reduced HDL to the active form of the disease. Although in vitro models of Leishmania-infected macrophages contributed to understanding of host-parasite lipid interactions, most were focused on cholesterol transport, leaving critical gaps in understanding how intracellular amastigotes exploit host lipids for proliferation and survival. In this study, in L. infantum promastigote-infected human THP-1 macrophages, we performed untargeted lipidomics at two time points 0 and 24 h post-infection to comprehensively assess host cell lipidome modulations. Lipidomic analysis revealed profound alterations in lipid profiles (fold-change > 10), with enrichment of sterols, sphingolipids, and phospholipids that correlated with L. infantum biomass. Key findings include: (i) rapid and massive host-to-parasite lipid transfer; (ii) intense remodeling of exogenous fatty acids into polyunsaturated species; and (iii) depletion of mitochondrial lipids and glycosphingolipids in macrophages. Notably, the infected macrophage lipidome exhibited a biphasic regulation, characterized by initial amastigote biomass synthesis followed by post-proliferative lipid storage accumulation. These results deepen our understanding of lipids' central role in VL pathogenesis, suggesting an intertwined relationship between uptake mechanisms, immune evasion and host clinical conditions.