Schematic to illustrate the pathogenesis of periodontitis. The dental plaque biofilm is complex, dynamic, and variable; it is subject to quantitative and qualitative ecological shifts in response to changes in the local environment (e.g., pH changes), changes in localised immune regulation, and extrinsic factors such as smoking. Bacteria in dental plaque signal the local tissue cells and immune cells via intrinsic and secreted microbe-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS) and specific antigens (e.g., fimbrial proteins). The healthy periodontium is maintained by an effective innate response to a commensal (nonpathogenic) microflora in dental plaque which is restricted to the gingival/plaque margin and in which neutrophils play a pivotal role regulated by low levels of cytokines such as IL-1β and IL-8. An ecological shift in dental plaque towards a more pathogenic microflora dominated by species such as Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia leads to an enhanced immune response through enhanced stimulation of cytokine responses from a wide range of periodontal and immune cells. The development of periodontitis is driven by an exaggerated activation of intrinsic periodontal cells, a heightened primary and thereafter secondary cytokine response leading to activation of innate effector responses and in particular recruitment and activation of neutrophils (in response to elevated IL-1β and IL-8) and osteoclasts (in response to RANKL). Enhanced local activity of neutrophils in the periodontium is reflected by increased levels of MMP-8 (neutrophil collagenase), MMP-9 (neutrophil gelatinase), and β-glucuronidase among other enzymes. Activated macrophages and T- and B-lymphocytes may also contribute to the cytokine milieu through secretion of TNF-α, IL-12, IL-17, and IL-18 and the balance of these proinflammatory cytokines with immunosuppressive mediators such as IL-10 and TGF-β may be an important determinant of disease progression. Persistence of this proinflammatory response, coupled with aberrant resolution, leads to tissue destruction characteristic of periodontitis which involves loss of the soft connective tissues of the periodontium (lamina propria of the gingiva and the periodontal ligament) and alveolar bone which eventually leads to compromised tooth function. The presentation and progress of periodontitis are influenced by a number of secondary factors such as age, smoking, coexisting metabolic disorders (e.g., diabetes, obesity), and genetic susceptibility.
