Neutrophil in sepsis: functional aberration and regulated cell death

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and is a leading cause of death in critically ill patients. Studies have shown that immune dysfunction plays a central role in the pathogenesis of sepsis. As key effector cells of innate immunity, neutrophils play an important role in the development of sepsis-associated immune dysfunction. In the septic state, neutrophils mainly exhibit functional abnormalities and aberrant activation of cell death pathways. Among these, the inhibition of neutrophil apoptosis is considered a major contributor to excessive inflammatory responses. Meanwhile, with continuous advances in research, other forms of neutrophil cell death such as necroptosis, pyroptosis, and NETosis have also been confirmed to be closely associated with the onset and progression of sepsis. Over the years, various strategies have been devised and effectively implemented to ameliorate aberrant immune responses during the progression of sepsis, including modulation of neutrophil function and death. This review will outline the functional alterations and cell death patterns of neutrophils in the septic state, with a focus on recent research advances in targeting neutrophils to regulate the host immune response following septic challenge, aiming to provide new insights for the treatment of sepsis.