Lena Völlger and Maren von Köckritz-Blickwede
In 2004, neutrophil extracellular traps (NETs) were described as a basic immune defense of neutrophils against various microbes. Since then, publications describing the stimuli and cellular mechanisms that can induce cells to release NETs have been accumulating. However, it is not yet fully clear whether NET formation starts as a single cell event that spreads through cell-to-cell communication or whether neighboring cells undergo NET formation simultaneously through a common trigger. Using immunofluorescence microscopy, we show here that at lower cell density, only single cells were detected releasing NET structures. However, the higher the cell density, the higher the fold increase in NET formation in PMA-stimulated cells compared to unstimulated cells. This may indicate that NET formation starts as a single cell event but can spread through cell communication. To fully understand the mechanisms mediating NET formation, future experiments should focus on single-cell analysis to characterize the detailed cellular events that mediate NET formation in individual cells within a population and to differentiate the signaling process leading to NET formation as opposed to other antimicrobial strategies such as phagocytosis or degranulation.