歯周病原細菌に対する自然免疫応答がもたらす慢性炎症と生体バリア破綻

抄録

 Periodontal disease is one of the major diseases afflicting human beings and is caused by a bacterial infection leading to gingival inflammation, periodontal tissue destruction, alveolar bone loss, and eventually to tooth loss. Chronic periodontitis is one of the major periodontal diseases, and the periodontal pathogen Porphyromonas gingivalis is frequently isolated from diseased sites in the patients with this disease. The major virulence factors produced by P. gingivalis induce cysteine proteinases, gingipains. We found that gingipains cleave CD14 on human monocytes and human gingival fibroblasts and ICAM-1 on human gingival epithelial cells, resulting in immune evasion by the bacterium in periodontal tissues. Furthermore, gingipains are capable of inducing the production of proinflammatory molecules, such as IL-33 by human gingival epithelial cells, and IL-31 by human mast cells. Porphyromonas gingivalis-induced IL-33 and IL-31 attenuated the production of LL-37, an antimicrobial peptide, and the expression of claudin-1, a tight junction molecule, respectively, in gingival epithelial cells. These findings suggest that IL-33 and IL-31 induced by gingipains resulted in the induction of chronic inflammation and the dysfunction of epithelial barrier. On the basis of our findings, the pathogenicity of gingipains is divided into two phases : (a) the acute inflammation during severe infection, where P. gingivalis produces a large amount of gingipains resulting in the proteolytic degradation of the host molecules, and (b) chronic inflammation during mild infection, where P. gingivalis produce a small amount of gingipains, resulting in the induction of chronic inflammatory conditions and the consequent impairment of innate immunity.