Hyper-inflammatory response in burn patients coincides with impaired antibacterial activity of neutrophils in blood and burn tissue

Burn injury is frequently complicated by excessive inflammation and bacterial infection, contributing to increased morbidity and delayed recovery. Neutrophils play a central role in antibacterial defense, yet their functional state after burn injury remains incompletely understood. This study investigated how burn injury affects neutrophil phenotype and antibacterial activity. In this prospective observational cohort study, neutrophils were isolated from blood and burn tissue (eschar) of burn patients and compared with blood neutrophils from healthy volunteers. Using multicolor flow cytometry and functional assays, we assessed neutrophil phenotype, phagocytosis of heat-killed FITC-labeled Staphylococcus aureus, migration, reactive oxygen species (ROS) production, and cytokine secretion. Burn tissue neutrophils (15 ± 7 days post burn) displayed increased degranulation, reflected by elevated expression of the activation markers CD11b, CD63, and CD66b, but showed markedly reduced antibacterial activity compared with healthy blood neutrophils. In both circulating and burn tissue neutrophils, phagocytosis of S. aureus strains was reduced by 50%, while intracellular ROS production was reduced by 2-fold (burn tissue) or 10-100-fold (blood). In burn tissue neutrophils, IL-8-induced migration was reduced by approximately 30%. Time-course experiments demonstrated that burn tissue neutrophils produced minimal ROS under both basal and PMA-stimulated conditions, indicating a profound defect in inducible oxidative burst capacity. Cells in burn tissue released inflammatory cytokines including MCP-1, IP-10, IL-8, IL-10, and IL-6, although levels were not significantly different from cells in healthy skin. These findings demonstrate that burn injury induces a dysfunctional neutrophil state characterized by phenotypic activation but impaired antibacterial function in both circulating and tissue-derived neutrophils. This dysfunctional response is likely to contribute to increased susceptibility to S. aureus infection, as well as impaired wound healing after burn injury, highlighting neutrophil dysfunction as a potential target to improve both post-burn infection control and clinical outcomes.