Macrophage polarization in sepsis: Emerging role and clinical application prospect

Abstract

Sepsis is a severe, potentially fatal condition defined by organ dysfunction due to excessive inflammation. Its complex pathogenesis and poor therapeutic outcomes pose significant challenges in treatment. Macrophages, with their high heterogeneity and plasticity, play crucial roles in both the innate and adaptive immune systems. They can polarize into M1-like macrophages, which promote pro-inflammatory responses, or M2-like macrophages, which mediate anti-inflammatory responses, positioning them as critical mediators in the immune response during sepsis.Macrophages are the main regulators of inflammatory responses, and their polarization is also regulated by inflammatory signaling pathways. This review highlights recent advances in the inflammatory signaling pathways involved in sepsis, mechanism of macrophage polarization mediated by inflammation-related signaling pathways in sepsis, and the role of signaling pathway mediated macrophage polarization in organ dysfunction involved in sepsis. We also explore the therapeutic potential of targeting macrophage polarization for immunotherapy, offering new perspectives on macrophage-targeted treatments for sepsis.