Glycolytic reprogramming and immune responses in macrophages: a crosstalk driven by bacterial infection

Macrophage glycolytic reprogramming during bacterial infection is a recognized metabolic shift with profound yet incompletely defined immunological consequences. This review delineates how this metabolic remodeling extends beyond energy provision to function as an integral immunoregulatory platform. We systematically examine the dual roles of key metabolic components, including the conformational dynamics of pyruvate kinase M2 that couple metabolic flux with inflammatory gene transcription, and the NAD⁺/NADH ratio that balances inflammasome activation against interferon responses. The review further explores how metabolites like lactate, succinate, and itaconate mediate immunomodulation through novel post-translational modifications, including histone lactylation and protein succinylation. Crucially, we analyze how diverse bacterial pathogens such as Salmonella and Mycobacterium tuberculosis exploit these metabolic networks for immune evasion. By integrating recent advances in host immunometabolism with bacterial pathogenesis, this work not only deciphers critical molecular dialogues at the host-pathogen interface but also identifies novel targetable pathways, offering a conceptual framework for developing innovative therapeutic strategies against persistent and antibiotic-resistant infections.