Evolution of macrophage function in sepsis-induced cardiomyopathy: Cellular networks from immune imbalance to myocardial injury

Sepsis-induced cardiomyopathy (SICM) is an acute, often reversible myocardial depression driven by the host response to infection. Cardiac macrophages are central signaling hubs that integrate systemic danger signals and orchestrate myocardial dysfunction. We introduce a "Macrophage Functional Continuum" model, conceptualizing macrophages as dynamic signal integrators undergoing three interconnected phases: sensing and initiation, intrinsic reprogramming and fate determination, and multicellular network execution. Conceptually, these phases represent functional modules that may overlap in time and vary across organs, rather than a rigid chronological sequence. Stage-matched strategies-including immunometabolic modulation, checkpoint control, nanomedicine, and macrophage-based therapies-may provide a more context-sensitive therapeutic framework than conventional anti-inflammatory approaches. This review aims to reframe macrophage biology in SICM and provide a roadmap for translational research.