Journal of Innate Immunity · Published 2025-06-11 · DOI 10.1159/000546476
<p>Background: As sentinel cells of innate immunity, macrophages exhibit microenvironment-driven functional plasticity critical for immune regulation and tissue homeostasis, yet maladaptive metabolic reprogramming-induced polarization dysregulation exacerbates disease progression by manifesting immune dysfunction. Summary: This review systematically deciphers the metabolic signatures governing macrophage polarization – spanning amino acid metabolism, glycolytic flux, lipid dynamics, and iron homeostasis – while dissecting how pathological microenvironments (encompassing tumor niches, atherosclerotic plaques, and obese adipose tissue) co-opt these pathways to drive pathogenesis. Crucially, this analysis demonstrates that cellular metabolism dictates macrophage phenotypic/functional states across disease contexts, with comprehensive decoding of their metabolic networks emerging as imperative for developing next-generation immunotherapies. Key Messages: Therapeutically, pathogenic polarization may be reversed through strategic interventions targeting metabolite-sensing receptors, pharmacologically blocking metabolic checkpoints, and reprogramming core metabolic modalities to restore immunoregulatory competence. </p>
Abstract from DOAJ. Public domain (CC0 1.0).
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