摘要：SummaryLeishmaniaparasites use elaborate virulence mechanisms to invade and thrive in macrophages. These virulence mechanisms inhibit host cell defense responses and generate a specialized replicative niche, the parasitophorous vacuole. In this work, we performed a genome-wide RNAi screen inDrosophilamacrophage-like cells to identify the host factors necessary forLeishmania amazonensisinfection. This screen identified 52 conserved genes required specifically for parasite entry, including several components of the SUMOylation machinery. Further studies in mammalian macrophages found thatL. amazonensisinfection inhibited SUMOylation within infected macrophages and this inhibition enhanced parasitophorous vacuole growth and parasite proliferation through modulation of multiple genes especiallyATP6V0D2, which in turn affectsCD36expression and cholesterol levels. Together, these data suggest that parasites actively sabotage host SUMOylation and alter host transcription to improve their intracellular niche and enhance their replication.Graphical abstractDisplay OmittedHighlights•Drosophilaused as discovery platform to probeLeishmania-macrophage interactions•In mammalian macrophages, amastigotes potently inhibit protein SUMOylation•Inhibition of SUMOylation favors amastigote proliferation within macrophages•ATP6V0D2expression and cholesterol levels increase to support amastigote growthImmunology, Parasitology
