Metabolic adaptations driving innate immune memory: mechanisms and therapeutic implications

Immune memory is a hallmark of the adaptive immune system. However, recent research reveals that innate immune cells also retain memory of prior pathogen exposure that prompts enhanced responses to subsequent infections. This phenomenon is termed "innate immune memory" or "trained immunity." Notably, remodeling of cellular metabolism, which closely links to epigenetic reprograming, is a prominent feature of innate immune memory. Adaptations in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, glutaminolysis, and lipid synthesis pathways are critical for establishing innate immune memory. This review provides an overview of the current understanding of how metabolic adaptations drive innate immune memory. This understanding is fundamental to understanding innate immune system functions and advancing therapies against infectious diseases.