Interorgan transfer of intact micron-sized lipid droplets to macrophages during the Drosophila immune response

Abstract

Abstract Macrophages are white blood cells of the immune system in both mammals and Drosophila. In addition to their roles in engulfing and killing microbial invaders by phagocytosis, these cells play important roles in embryonic development, tissue repair, metabolism, and maintenance of homeostasis. Under certain inflammatory conditions, mammalian macrophages accumulate lipids in the form of lipid droplets, including in infection, atherosclerosis, and obesity; however, neither the mechanisms nor purpose of this accumulation are well-understood. We have found that fly macrophages also accumulate lipid droplets, with astonishing speed following bacterial infection: filling up to 30% of cell volume within 3 hrs of infection. We have discovered a completely novel mechanism for this inflammatory lipid accumulation: instead of synthesizing lipids from fatty acids or glucose taken up from the blood, fly macrophages obtain intact, micron-sized lipid droplets from the adipose tissue, through a phagocytosis-like mechanism we term “phagoliposis”. By genetically blocking the metabolism of these lipid droplets, we have discovered some important inflammatory mechanisms fueled by these lipids. Supported by grants from NIH (SC2AI133653)