The NET, the trap and the pathogen: neutrophil extracellular traps in cutaneous immunity

Abstract

Neutrophil extracellular traps (NETs), large chromatin structures casted with various proteins, are externalized by neutrophils upon induction by both self-and non-self-stimuli. It has become clear that NETs are potent triggers of inflammation in autoimmune skin diseases. Moreover, the ability of NETs to trap pathogens suggests a crucial role in innate host defense. However, the outcome of the encounter between pathogens and NETs remains highly controversial. Here, we discuss recent insights into the morphology and formation of NETs, their role in skin inflammation and how NETs might contribute to host protection in skin infection.

Dimethyl fumarate modulates neutrophil extracellular trap formation in a glutathione‐ and superoxide‐dependent manner

“…It was previously reported that dysfunction of GSH reductase – and thus reduced levels of GSH – impairs PMN oxidative burst capacity . Along this line, DMF significantly reduced production of PMA‐induced ROS whose release constitutes a critical early event in many forms of NET formation (see Stephan et al . and Hoffmann and Enk).…”

“…Generation of reactive oxygen species (ROS) is thought to possess a pivotal role in early NADPH oxidase (Nox)‐dependent NET formation (see Stephan et al . and Hoffman and Enk).…”

“…Furthermore, PMN were reported to represent one of the main groups of interleukin (IL)‐17 positive cells in developed psoriatic plaques and in vivo models of human skin inflammation . Neutrophil extracellular trap (NET) formation by PMN, first described by Brinkmann et al ., results in the extracellular presentation of opsonized self‐DNA (see Stephan et al . and Hoffmann and Enk).…”

Neutrophil Extracellular Traps of Cynoglossus semilaevis: Production Characteristics and Antibacterial Effect

“…Neutrophils from patients with mutations in NADPH oxidase and knockout mice that lacked functional NADPH oxidase failed to produce NETs in response to PMA (12, 13); NETs formation upon activation with bacteria was also impaired after pharmacological inhibition of respiratory burst with NADPH oxidase inhibitor (2). The underlying mechanism is that ROS is able to activate PAD4, which in turn mediates the citrullination of histone and results in chromatin decondensation, which is an essential of NETosis (5). Besides ROS, NO is another key player in NET formation both in human and mouse neutrophils (26, 27).…”

“…NETs are web-like structures composed of extracellular DNA, histones, and antimicrobial proteolytic enzymes in the granules of neutrophils, such as neutrophil elastase and myeloperoxidase (MPO) (4). NETs have been reported to capture and immobilize bacteria; however, there is much controversy about whether NETs can directly kill bacteria (5). …”