Impaired Porphyromonas gingivalis–Induced Tumor Necrosis Factor Production by Dendritic Cells Typifies Patients With Rheumatoid Arthritis

Kim C M Santegoets, Mark H Wenink, Felipe A Vieira Braga, Marta Cossu, Femke B G Lamers-Karnebeek, Piet L C M van Riel, Patrick D J Sturm, Wim B van den Berg, Timothy R D J Radstake

The prevalence of periodontitis is increased in rheumatoid arthritis (RA) patients and the severity of periodontitis can affect the level of arthritis. Porphyromonas gingivalis is one of the main bacteria involved in periodontitis. Our aim was to determine if there are differences in the innate immune response against P. gingivalis between healthy controls and RA patients. Monocyte-derived dendritic cells (DCs) from healthy controls, RA and psoriatic arthritis patients were stimulated with P. gingivalis, a range of other bacteria and TLR agonists. Cytokine production was determined and blocking studies were performed to determine which receptors were involved in differential recognition of P. gingivalis. Effects on T cell cytokines were also determined in PBMC cultures. Upon stimulation with P. gingivalis RA DCs produced less TNFα as compared to healthy control DCs, an observation that was not present in patients with psoriatic arthritis nor upon stimulation with other bacteria. In addition, P. gingivalis mediated activation of RA PBMCs showed a clear reduction of IFNγ production. From the various possibly underlying mechanisms investigated, only blockade of complement receptor 3 (CR3) abolished the difference between RA patients and healthy controls, suggesting the involvement of CR3 in this process. Immune cells from RA patients display a reduced response to P. gingivalis which has functional consequences for the immune response. This may result in prolonged survival of P. gingivalis possibly driving autoantibody formation and a self-perpetuating loop of chronic inflammation. The possible role of CR3 therein warrants further investigation. This article is protected by copyright. All rights reserved.