Oral Porphyromonas Gingivalis Infection Increases Arthritis Severity and Progression.

Abstract

Periodontitis is a polymicrobial oral infection characterized by the destruction of tooth supporting structures that may influence rheumatoid arthritis. Porphyromonas gingivalis (P. gingivalis), a bacterium implicated in the etiology of periodontitis, has shown variation in inducing T-cell responses depending on the clinical strain. In this study, we determined the differences between the systemic responses of different P. gingivalis strains that have important clinical representation. We also determined the effect of chronic periodontal disease on immune activation during collagen-induced arthritis (CIA) development in mice. Our results confirmed that the strains of P. gingivalis A7A1-28, W50, and W83 had the ability to colonize the oral cavity of mice, induce periodontal disease, and change the expression profile of splenocytes. We found that splenic anti-inflammatory IL-10 expression was associated with the least amount of alveolar bone loss. Our results showed that P. gingivalis had the ability to activate dendritic cells and express IL-12, IL-6, and TGF-β in vitro. Orally, P. gingivalis induced a local Thelper (h)1-Th2-Treg response. CIA immunizations also resulted in periodontal bone loss. Prior P. gingivalis oral infection resulted in a trend for increased serum Th17/IFN-γ ratio and increased splenocyte numbers (splenomegaly) in mice induced for collagen-induced arthritis. In the complete Freund’s adjuvant (CFA) model, P. gingivalis infection induced a greater number of osteoclasts and tissue swelling once arthritis affected the entire paw in the CFA model of disease. In the incomplete Freund’s adjuvant (IFA) model for arthritis, P. gingivalis increased pannus formation, bone destruction, and osteoclast numbers. Together, our results indicate that chronic oral infection with P. gingivalis prior to arthritis induction altered Th cell-mediated responses and increased Th17 responses in collagen-induced arthritic mice. These results are important in furthering our understanding for the potential of an oral chronic infection in altering arthritis in susceptible patients, and may have important implications for developing future preventive periodontal and RA therapies.