Targeting Neutrophils in Sepsis: From Mechanism to Translation

Abstract

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Although our understanding in the pathophysiological features of sepsis has increased significantly during the past decades, there is still lack of specific treatment for sepsis. Neutrophils are important regulators against invading pathogens, and their role during sepsis has been studied extensively. It has been suggested that the migration, the antimicrobial activity, and the function of neutrophil extracellular traps (NETs) have all been impaired during sepsis, which results in an inappropriate response to primary infection and potentially increase the susceptibility to secondary infection. On the other hand, accumulating evidence has shown that the reversal or restoration of neutrophil function can promote bacterial clearance and improve sepsis outcome, supporting the idea that targeting neutrophils may be a promising strategy for sepsis treatment. In this review, we will give an overview of the role of neutrophils during sepsis and discuss the potential therapeutic strategy targeting neutrophils.

Keywords: Signaling pathway; neutrophil; sepsis; therapeutic target; translational medicine.

FIGURE 1

Schematic depicting current knowledge in the pathophysiological features of neutrophils during sepsis. During sepsis, both mature and immature neutrophils are generated in the bone marrow and are mobilized into peripheral blood. Transcriptional factors and environmental stimulus that determine the phenotypes of neutrophils presented in sepsis are largely unknown. Several pathophysiological features related to neutrophil function have been described, including dysregulated migration capacity, impaired antimicrobial activity, and suppression of adaptive immunity through the expression of inhibitory immune checkpoints. Neutrophil extracellular traps (NETs) in sepsis are also not controlled properly, and play an important role in tissue damage and coagulation disturbance.