Immunological aspects of the pathophysiology of periodontitis

Periodontitis is a multifactorial chronic inflammatory disease of the tooth-supporting tissues leading to alveolar bone loss and tooth exfoliation. In this condition, there is an increased influx of polymorphonuclear leukocytes (PMNs) into the oral cavity. Oral PMNs showed to have antimicrobial capacities by their ability to internalize microbes (phagocytosis) and the hyper(re)active neutrophil extracellular trap (NET) formation.
In the blood circulation, NET accumulation (e.g. caused by reduced NET degradation) may negatively affect various chronic conditions such as cardiovascular disease. Interestingly, we observed that non-surgical periodontal therapy partly restored the reduced NET degradation and this was maintained for 3, 6, and 12 months.
The chronic immune cell infiltration of the inflamed periodontal soft tissues in periodontitis is accompanied by osteoclast-induced alveolar bone resorption, the hallmark of periodontitis progression. Despite the fact that PMNs are abundantly present in inflamed tissues, neither oral PMNs nor circulatory PMNs contributed to osteoclast formation, while gingival fibroblasts have osteoclastogenic capacities. These gingival fibroblasts also contribute to both the temporization and clearance of gingival inflammation by supporting the long-term survival and even proliferation of leukocytes (T, B, NK cells and monocytes) which are present in these inflamed periodontitis lesions. Notably, the T-cell proliferation was also shown to be stimulated via persistently present Toll-like Receptor agonists. Thus, the gingival fibroblasts are suggested to maintain and possibly worsening the periodontal inflammation, which may explain the chronicity of periodontitis.