title: Impaired Porphyromonas gingivalis-Induced Tumor Necrosis Factor Production by Dendritic Cells Typifies Patients With Rheumatoid Arthritis.
abstract: OBJECTIVE
  The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA), 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.
  
  
  METHODS
  Monocyte-derived dendritic cells (DCs) from healthy controls, RA patients, and patients with psoriatic arthritis (PsA) were stimulated with P gingivalis, a range of other bacteria, and Toll-like receptor 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 cultures of peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  Upon stimulation with P gingivalis, RA patient DCs produced less tumor necrosis factor as compared to healthy control DCs, which was not observed in PsA patients or upon stimulation with other bacteria. In addition, P gingivalis-mediated activation of RA patient PBMCs showed a clear reduction of interferon-γ production. Among the various possible underlying mechanisms investigated, only blockade of CR3 abolished the difference between RA patients and healthy controls, suggesting the involvement of CR3 in this process.
  
  
  CONCLUSIONS
  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 in this process warrants further investigation.
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands, and Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kim C M
authors.initials: KC
authors.lastname: Santegoets
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands, and Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wenink
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Felipe A Vieira
authors.initials: FA
authors.lastname: Braga
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marta
authors.initials: M
authors.lastname: Cossu
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Femke B G
authors.initials: FB
authors.lastname: Lamers-Karnebeek
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Patrick D J
authors.initials: PD
authors.lastname: Sturm
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015535:Arthritis, Psoriatic / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000276:immunology*; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016966:Porphyromonas gingivalis; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D016177:Macrophage-1 Antigen; C439524:TNF protein, human; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma