Neutrophil Extracellular Traps Exert Potential Cytotoxic and Proinflammatory Effects in the Dental Pulp

Abstract Introduction Neutrophil extracellular traps (NETs) are an important innate immune mechanism aimed at limiting the dissemination of bacteria within tissues and localizing antibacterial killing mechanisms. There is significant interest in the role of NETs in a range of infectious and inflammatory diseases; however, their role in diseased pulp has yet to be explored. Our aim was to determine their relevance to infected pulp and how their components affect human dental pulp cell (HDPC) responses. Methods Diseased pulp tissue was stained for the presence of extracellular DNA and elastase to detect the presence of NETs. Bacteria known to infect pulp were also assayed to determine their ability to stimulate NETs. Coculture studies and NET component challenge were used to determine the effect of extracellular NET release on HDPC viability and inflammatory response. NET-stimulated HDPC secretomes were assessed for their chemotactic activity for lymphocytes and macrophages. Results Data indicate that NETs are present in infected pulp tissue and whole NETs, and their histone components, particularly H2A, decreased HDPC viability and stimulated chemokine release, resulting in an attraction of lymphocyte populations. Conclusions NETs are likely important in pulpal pathogenesis with injurious and chronic inflammatory effects on HDPCs, which may contribute to disease progression. Macrophages are chemoattracted to NET-induced apoptotic HDPCs, facilitating cellular debris removal. NETs and histones may provide novel prognostic markers and/or therapeutic targets for pulpal diseases.