The Dual Role of Macrophage Extracellular Traps in Host Defense and Disease: Mechanisms and Therapeutic Implications

Abstract

Macrophage extracellular traps (METs), which are extracellular immune structures released by macrophages, consist primarily of double-stranded DNA, histones, elastase, matrix metalloproteinase, myeloperoxidase, and other components. Recent studies have found that various pathogens (such as bacteria, fungi, and parasites) and environmental pollutants could induce the formation of METs through different mechanisms to help the host resist infection. However, accumulating evidence suggests that METs play a double-edged role in immune response, enhancing host defense while potentially contributing to tissue damage under certain pathological conditions. This review summarizes the mechanisms underlying the formation of METs, including different pathways triggered by various pathogens and environmental pollutants. We also discussed the role of METs in respiratory diseases, autoimmune diseases, metabolic diseases, tumors, and transplantation and injury, as well as recent advances in MET-targeted drugs, aiming to provide new insights for improving treatment strategies of relevant diseases.