Exploring the mechanism of polymorphonuclear neutrophils against sepsis based on immune model.

BACKGROUND

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and remains a major global health challenge. Polymorphonuclear neutrophils (PMNs), as major effectors of innate immunity, are essential for antimicrobial defense but can also contribute to immune dysregulation, tissue injury, and organ failure during sepsis.

METHODS

We conducted a narrative review of the literature by searching PubMed and Web of Science from database inception to November 2025. Search terms included sepsis, septic shock, neutrophils, polymorphonuclear neutrophils, PMNs, immunology, immune models, diagnosis, biomarkers, and treatment. Peer-reviewed English-language studies and reviews focusing on neutrophil biology, immune mechanisms, diagnostic applications, and therapeutic strategies in sepsis were included.

RESULTS

Current evidence shows that PMNs play a dual role in sepsis. On the one hand, they mediate pathogen clearance through chemotaxis, phagocytosis, reactive oxygen species production, degranulation, and neutrophil extracellular trap formation. On the other hand, excessive or dysregulated PMN activation amplifies inflammation, disrupts endothelial and microvascular integrity, alters cellular metabolism, and promotes organ dysfunction. Sepsis is also associated with marked neutrophil phenotypic and functional changes, including altered surface marker expression, impaired migration and phagocytosis, glycolytic reprogramming, and abnormal intercellular signaling. Emerging biomarkers, immune-related prognostic models, and artificial intelligence-assisted approaches may improve risk stratification and individualized management.

CONCLUSIONS

PMNs are central to the immunopathogenesis of sepsis and represent promising biomarkers and therapeutic targets. Further studies on neutrophil heterogeneity, metabolic adaptation, and immune interactions may support the development of more precise diagnostic and immunomodulatory strategies.