{"title":"Neutrophil extracellular traps in sepsis: Trade-off between pros and cons","authors":"Fengying Liao, Jiangbo Fan, Rui Wang, Zhe Xu, Qinyuan Li, Wanda Bi, Jin Deng, Jianxin Jiang, Zhen Wang, Ling Zeng","doi":"10.1093/burnst/tkaf046","DOIUrl":null,"url":null,"abstract":"Sepsis, a life-threatening syndrome driven by dysregulated immune responses to infection, presents significant global health challenges with high mortality rates. Neutrophil extracellular traps (NETs), composed of DNA and antimicrobial proteins, play a dual role in sepsis pathogenesis. While NETs trap pathogens and enhance immune responses via antimicrobial activity and immune cell activation, their overproduction exacerbates tissue damage, coagulopathy, and organ dysfunction. This review explores the mechanisms of NET formation, including suicidal, vital, and noncanonical NETosis, and their regulation through pattern recognition receptors, complement systems, and chemokine signaling. The interplay between NETs and immune cells—such as macrophages, T cells, and platelets - is highlighted, emphasizing NETs' role in both pathogen clearance and inflammatory injury. Excessive NETs contribute to sepsis-associated coagulopathy by activating platelets and damaging endothelial cells, while histones and proteases within NETs mediate cytotoxicity. Emerging therapeutic strategies targeting NETs, such as DNase, PAD4 inhibitors, and anti-inflammatory agents, show promise in preclinical studies but face clinical challenges due to their dual roles and off-target effects. Balancing NETs' protective and pathological functions remains critical for sepsis management. This review aims to provide a comprehensive understanding of NETs in sepsis, offering insights for future research and clinical applications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"29 1","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Burns & Trauma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/burnst/tkaf046","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Sepsis, a life-threatening syndrome driven by dysregulated immune responses to infection, presents significant global health challenges with high mortality rates. Neutrophil extracellular traps (NETs), composed of DNA and antimicrobial proteins, play a dual role in sepsis pathogenesis. While NETs trap pathogens and enhance immune responses via antimicrobial activity and immune cell activation, their overproduction exacerbates tissue damage, coagulopathy, and organ dysfunction. This review explores the mechanisms of NET formation, including suicidal, vital, and noncanonical NETosis, and their regulation through pattern recognition receptors, complement systems, and chemokine signaling. The interplay between NETs and immune cells—such as macrophages, T cells, and platelets - is highlighted, emphasizing NETs' role in both pathogen clearance and inflammatory injury. Excessive NETs contribute to sepsis-associated coagulopathy by activating platelets and damaging endothelial cells, while histones and proteases within NETs mediate cytotoxicity. Emerging therapeutic strategies targeting NETs, such as DNase, PAD4 inhibitors, and anti-inflammatory agents, show promise in preclinical studies but face clinical challenges due to their dual roles and off-target effects. Balancing NETs' protective and pathological functions remains critical for sepsis management. This review aims to provide a comprehensive understanding of NETs in sepsis, offering insights for future research and clinical applications.
期刊介绍:
The first open access journal in the field of burns and trauma injury in the Asia-Pacific region, Burns & Trauma publishes the latest developments in basic, clinical and translational research in the field. With a special focus on prevention, clinical treatment and basic research, the journal welcomes submissions in various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, and the prevention and regeneration of burns and trauma injuries. With an expert Editorial Board and a team of dedicated scientific editors, the journal enjoys a large readership and is supported by Southwest Hospital, which covers authors'' article processing charges.