2026/05/21 by Daewon Lee, Ferdinand Koranteng, Nuri Cha +5 · 1 voice
Immunology and Microbiology · Neuroscience · #Invertebrate Immune Response Mechanisms #Neurobiology and Insect Physiology Research #interferon and immune responses
paper · pdf · doi:10.7554/elife.111341
openalex publication_date 2026/05/21 · openalex created_date 2026/05/22 · openalex updated_date 2026/08/01
Innate immune cells rapidly reprogram their metabolism upon activation, yet the metabolic basis of this flexibility in invertebrate systems remains largely unexplored. Here, we investigate the metabolic landscape of Drosophila larval hemocytes, functional analogs of vertebrate myeloid cells, across developmental stages, genotypes, and immune activation states, by combining metabolic flux measurements with single-cell transcriptomics. Under homeostatic conditions, hemocytes rely predominantly on mitochondrial oxidative phosphorylation for ATP production, with minimal glycolytic contribution. Immune activation, particularly lamellocyte differentiation, drives enhanced mitochondrial respiration and metabolic flexibility, accompanied by structural remodeling of the mitochondrial network. Mechanistically, functional lamellocytes require Drp1-mediated mitochondrial fission and utilize glucose and trehalose as primary carbon sources to sustain mitochondrial respiration, which is essential for effective immune responses. Overall, these findings establish that mitochondrial metabolic reprogramming is a conserved feature of innate immune activation in myeloid-like immune cells and reveal an evolutionarily ancient link between mitochondrial dynamics and immune cell activation, with implications for understanding metabolic regulation of innate immunity in invertebrate models and beyond.