The role of neutrophils in the mechanisms of sepsis

The international consensus Sepsis-3 in 2016 defined sepsis as life-threatening organ dysfunction caused by a disruption of the host response to infection. One of the main mechanisms leading to the death of patients with sepsis is an imbalance of the immune response to pathogens. Activation of immune cells, in particular neutrophils, plays a key role in the mechanisms of sepsis. During sepsis, the number of immature neutrophils in the blood increases, PD-L1 neutrophils appear, which have an immunosuppressive function, and the number of Neu1 subtype of neutrophils, characterized by high expression of the NF-kB inhibitor, the chemokine CXCL8, olfactomedine, which regulates the production of cytokines, and myeloperoxidase, increases. When the inflammatory response generalizes, the phagocytic and bactericidal functions of neutrophils are disrupted. An important role in the mechanisms of sepsis is played by the formation of neutrophil extracellular traps, extracellular DNA, and the nuclear non-histone protein HMGB1, which are DAMPs and have proinflammatory activity. The development of approaches to predicting the development and course of sepsis in injuries and infectious and inflammatory diseases based on assessing the functional activity of neutrophils and their phenotype is a promising area of research, in particular approaches to regulating the functioning of neutrophils using miRNA.