The role of neutrophil extracellular traps in the pathogenesis of periodontal diseases

Abstract

This thesis investigated neutrophil extracellular traps (NETs) in the pathogenesis of periodontal diseases, including chronic periodontitis, experimental gingivitis and Papillon Lefèvre syndrome (PLS). $In$ $vitro$ assays investigated the interactions between periodontal bacteria and peripheral neutrophils isolated by discontinuous Percoll gradients, and demonstrated differential NET release in response to bacteria. Interestingly, NETs entrapped all periodontal bacteria assayed to some extent; however bacterial growth and survival were not impeded. A longitudinal intervention clinical study of chronic periodontitis patients and matched healthy controls revealed no differences in peripheral NET production; however NET production by patients decreased following non-surgical treatment. Furthermore, a subset of patients displayed impeded NET degradation by plasma that was restored following disease treatment; this may be the result of increased circulating immunoglobulins and free light chains (FLCs) pre-treatment. Peripheral NET production did not change throughout the experimental gingivitis model study; however NET release was impeded in PLS patients relative to healthy controls. Additional $in$ $vitro$ studies demonstrated that cigarette smoking had an inhibitory effect on NET release. Collectively, this thesis indicates that NETs contribute to innate immunity, however, given that periodontitis pathogenesis is characterised by aberrant neutrophil responses, NETs may also be involved in the progression of the disease