Open Access Research article

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Julie Teresa Marchesan1, Elizabeth Ann Gerow1, Riley Schaff1, Andrei Dan Taut1, Seung-Yun Shin12, James Sugai1, David Brand3, Aaron Burberry4, Julie Jorns4, Steven Karl Lundy5, Gabriel Nuñez4, David A Fox5 and William V Giannobile1*

Author Affiliations

1 Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA

2 Department of Periodontology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, South Korea

3 Research Service, Veterans Affairs Medical Center, Memphis, TN, USA

4 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

5 Department of Internal Medicine – Division of Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA

For all author emails, please log on.

Arthritis Research & Therapy 2013, 15:R186  doi:10.1186/ar4376

Published: 12 November 2013

Abstract

Introduction

Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.

Methods

DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.

Results

Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.

Conclusions

Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.