Neutrophil Extracellular Traps (NETs): An Emerging Therapeutic Target to Improve Infectious Diseases Outcomes

Abstract Neutrophils possess a diverse repertoire of pathogen clearance mechanisms, one of which is the formation of neutrophil extracellular traps (NETs). NETs are complexes of histone proteins and DNA coated with proteolytic enzymes that are released extracellularly to entrap pathogens and aid in their clearance, in a process known as NETosis. Intravascular NETosis may drive a massive inflammatory response that has been shown to contribute to morbidity and mortality in many infectious diseases, including malaria, dengue fever, influenza, bacterial sepsis, and severe acute respiratory syndrome coronavirus 2 infection. In this review we seek to (1) summarize the current understanding of NETs, (2) discuss infectious diseases in which NET formation contributes to morbidity and mortality, and (3) explore potential adjunctive therapeutics that may be considered for future study in treating severe infections driven by NET pathophysiology. This includes drugs specifically targeting NET inhibition and US Food and Drug Administration–approved drugs that may be repurposed as NET inhibitors.