Hooked on fat: host lipid manipulation by protozoan Leishmania infantum

The protozoan, Leishmania infantum causes visceral leishmaniasis (VL), a neglected tropical disease. In active VL, we observe elevated triglyceride and very low-density lipoprotein (VLDL), and reduced high-density lipoprotein (HDL) levels, along with related gene polymorphisms identified as risk factors for the development of overt disease. To investigate the contribution of lipids to infection development, we performed untargeted lipidomics on L. infantum promastigote-infected human THP-1 macrophages and intracellular amastigotes at two time points. We detected unprecedented, profound alterations in lipid profiles with enrichment of sterols, sphingolipids, and phospholipids correlated with L. infantum infection. These changes suggest intense host-to-parasite lipid transfer, remodeling of exogenous fatty acids into polyunsaturated species in parasites, and depletion of mitochondrial lipids and glycosphingolipids in macrophages. Notably, we observed a biphasic regulation, characterized by the initial synthesis of amastigote biomass followed by the accumulation of post-proliferative lipid storage. These results deepen our understanding of lipids’ central role in parasite growth with implications for disease progression.