Lipid droplets restrict phagosome formation duringCandidachallenge

Abstract

SUMMARYLipid droplets (LDs) are intracellular organelles which can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages. However, the function of LDs in the phagocytosis remains elusive. Here, we unveil the role of LDs in modulating phagosome formation using a fungal infection model. Specifically, LDs accumulation restricted the quantity of phagosome formation, and protected macrophages from death. Mechanistically, LDs formation competitively consumed intracellular endoplasmic reticulum membrane and altered RAC1 translocation and its GTPase activity, which resulted in limiting phagosomes formation in macrophages during fungi engulfed. Mice withHilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection withC. albicans. Notably, administration of ATGL inhibitor Atglistatin improved host outcomes in disseminated fungal infections. Taken together, our study elucidates the mechanism of LDs in controlling phagosomes formation to avoid immune cell death, and offers a potential drug target for treatment ofC. albicansinfections.HighlightsC. albicansinfection induces triglycerides production and LD accumulation in macrophages.LD restricts the quantity of phagosome formation and protects macrophages from death.LD consumes intracellular ER membrane components and alters RAC1 translocation and its GTPase activity.Administration of ATGL inhibitor Atglistatin improves host outcomes in disseminated fungal infections.