Metabolic strategy of macrophages under homeostasis or immune stress in Drosophila

Macrophages are well known for their phagocytic functions in innate immunity across species. In mammals, they rapidly consume a large amount of energy by shifting their metabolism from mitochondrial oxidative phosphorylation toward aerobic glycolysis, to perform the effective bactericidal function upon infection. Meanwhile, they strive for sufficient energy resources by restricting systemic metabolism. In contrast, under nutrient deprivation, the macrophage population is down-regulated to save energy for survival. Drosophila melanogaster possesses a highly conserved and comparatively simple innate immune system. Intriguingly, recent studies have shown that Drosophila plasmatocytes, the macrophage-like blood cells, adopt comparable metabolic remodeling and signaling pathways to achieve energy reassignment when challenged by pathogens, indicating the conservation of such metabolic strategies between insects and mammals. Here, focusing on Drosophila macrophages (plasmatocytes), we review recent advances regarding their comprehensive roles in local or systemic metabolism under homeostasis or stress, emphasizing macrophages as critical players in the crosstalk between the immune system and organic metabolism from a Drosophila perspective.