Sleep-dependent clearance of brain lipids by peripheral blood cells

Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery^1,2. Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater-a member of the Nimrod receptor family-reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD⁺, is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.