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The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. The non-specific plaque hypothesis was the first attempt to explain the role of the dental biofilm in the pathogenesis of periodontal diseases. However, the introduction of sophisticated diagnostic and laboratory assays has led to the realisation that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the host’s immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis. This review aims to highlight the development and structure of the dental plaque biofilm and to explore current literature on the transition from a healthy (symbiotic) to a diseased (dysbiotic) biofilm in periodontitis and the associated immune-inflammatory responses that drive periodontal tissue destruction and form mechanistic pathways that impact other systemic non-communicable diseases. [ABSTRACT FROM AUTHOR]

Background: Aggressive periodontitis is associated with the presence of Aggregatibacter actinomycetemcomitans , a leukotoxin (Ltx)-producing periodontal pathogen. Ltx has the ability to lyse white blood cells including neutrophils., Objectives: This study was aimed at investigating the interactions between neutrophils and Ltx with regard to the chemotactic properties of Ltx and the release of neutrophil extracellular traps (NETs)., Methods: Neutrophils from healthy blood donors were isolated and incubated for 30 min and 3 h with increasing concentrations of Ltx (1, 10, and 100 ng/mL) as well as with A. actinomycetemcomitans strains (NCTC 9710 and HK 1651) producing different levels of Ltx. Formation of NETs and cell lysis were assessed by microscopy, fluorescence-based assays, and measurement of released lactate dehydrogenase. Neutrophil migration in response to different Ltx gradients was monitored by real-time video microscopy, and image analysis was performed using ImageJ software., Results: Although Ltx (10 and 100 ng/mL) and the leukotoxic A. actinomycetemcomitans strain HK 1651 lysed some neutrophils, other cells were still capable of performing NETosis in a concentration-dependent manner. Low doses of Ltx and the weakly leukotoxic strain NCTC 9710 did not lead to neutrophil lysis, but did induce some NETosis. Furthermore, all three concentrations of Ltx enhanced random neutrophil movement; however, low directional accuracy was observed compared with the positive control (fMLP)., Conclusions: The results indicate that Ltx acts both as a neutrophil activator and also causes cell death. In addition, Ltx directly induces NETosis in neutrophils prior to cell lysis. In future studies, the underlying pathways involved in Ltx-meditated neutrophil activation and NETosis need to be investigated further., Competing Interests: Conflict of interest and fundingThis study was financially supported by the German Society of Dental and Oral Medicine (DGZMK), the Västerbotten County of Sweden (TUA), and the University of Birmingham.