Neutrophil Extracellular Traps in Respiratory Disease: guided anti-microbial traps or toxic webs?

Neutrophil recruitment to the airways and lungs is a major hallmark of many respiratory diseases. One of the more recently discovered unique innate immune effector mechanisms of neutrophils is the formation of neutrophil extracellular traps (NETs), consisting of an extracellular network of DNA fibers studded with nuclear and granule proteins. Although in the respiratory system NETs contribute to capture and inactivation of bacteria, fungi and viruses, there is a delicate 'balance' between aid and damage to the host. Accumulating evidence now suggests that NETs can have direct cytotoxic effects to lung epithelial and endothelial cells and can contribute to airway obstruction. As such, NETs may play an important role in the pathogenesis of respiratory diseases. The purpose of this review is to give an up-to-date overview of the current status of NETs in respiratory diseases. We examine both experimental and clinical data concerning the role of NETs in host defence as well as immunopathology, with special attention paid to the literature relevant for the paediatric pulmonology community. Finally, we discuss future treatment strategies that may target the formation of NETs in the airways and lungs.