The critical role of neutrophil extracellular traps in pathological mineralization

Abstract Neutrophil extracellular traps (NETs) are initially perceived as bioactive webs for trapping pathogens to limit the spread of infection. Neutrophils suicidally release NETs upon stimulation by pathogens and other non-infectious factors such as micro-crystals. Here, the authors demonstrate, using in vitro and in vivo calculus mineralisation models, that NETs function as nucleation sites for mineralisation of calculus. The NETs are usually cleared by nucleases derived from the host’s body fluids or immune system. However, bacteria in the calculus microenvironment are capable of transforming NETs from the more common nuclease-susceptible B-form into the nuclease-resistant Z-form. The crosstalk between infection and the host immune system results in the development of calculus. These findings indicate that calculus formation may be controlled by regulating the NET-DNA configuration. The use of chloroquine for converting NET-Z-DNA into NET-B-DNA represents a new therapeutic solution for reducing the prevalence and recurrence of calculus in populations who are susceptible to the development of these ectopic mineralisation entities.