Immunometabolism drives metabolic and infectious disease progression through bidirectional metabolic reprogramming and epigenetic remodeling

Abstract

Immunometabolism has become a central mechanism governing innate and adaptive immune responses. The field has moved from cataloguing metabolic shifts during immune activation to understanding how specific pathways control immune cell fate and function. This review brings together current knowledge on immunometabolic regulation in metabolic and infectious diseases, emphasizing bidirectional crosstalk between these domains. We address controversies over whether inflammation causes insulin resistance or follows from it, examine the distinct metabolic programs of different immune cell types, and explore trained immunity as a link between innate immune memory and metabolic disease. The review also covers pathogen-specific metabolic strategies and host countermeasures, surveys emerging immunometabolic therapies, and flags unresolved questions for future work. Among promising strategies, mechanistic target of rapamycin (mTOR) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have advanced to clinical trials for immunometabolic indications, whereas epigenetic reprogramming and nanoparticle-based metabolic delivery remain in preclinical development.