Metabolic Control of Immunity-Unveiling Neutrophil Mechanisms

Immune metabolism is a central determinant of neutrophil development, plasticity, and function. Once considered strictly glycolytic, neutrophils are now recognized as metabolically flexible cells that dynamically engage glycolysis, the pentose phosphate pathway (PPP), amino acid metabolism, and lipid oxidation to meet energetic and biosynthetic demands. Neutrophil metabolism is tightly regulated by nutrient-sensing and stress-response pathways, including mTOR, AMPK, and HIF-1α, which integrate environmental cues such as hypoxia and nutrient deprivation. In disease, metabolic rewiring underlies functional dysregulation, highlighting its role in chronic inflammatory disorders, metabolic syndromes, infection, and cancer. Therefore, targeting neutrophil metabolism offers therapeutic potential by restoring homeostasis, reducing inflammation, or enhancing antimicrobial and anti-tumor responses. Altogether, understanding neutrophil metabolic plasticity provides critical insights into immune regulation in health and disease, and offers promising avenues for novel therapies in chronic inflammation, metabolic disorders, infection, and cancer.