title: Periodontitis-associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14(+) monocytes leading to enhanced Th17/IL-17 responses.
abstract: The Th17/IL-17 pathway is implicated in the pathogenesis of periodontitis (PD), however the mechanisms are not fully understood. We investigated the mechanism by which the periodontal pathogens Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) promote a Th17/IL-17 response in vitro, and studied IL-17(+) CD4(+) T-cell frequencies in gingival tissue and peripheral blood from patients with PD versus periodontally healthy controls. Addition of Pg or Aa to monocyte/CD4(+) T-cell co-cultures promoted a Th17/IL-17 response in vitro in a dose- and time-dependent manner. Pg or Aa stimulation of monocytes resulted in increased CD40, CD54 and HLA-DR expression, and enhanced TNF-α, IL-1β, IL-6 and IL-23 production. Mechanistically, IL-17 production in Pg-stimulated co-cultures was partially dependent on IL-1β, IL-23 and TLR2/TLR4 signalling. Increased frequencies of IL-17(+) cells were observed in gingival tissue from patients with PD compared to healthy subjects. No differences were observed in IL-17(+) CD4(+) T-cell frequencies in peripheral blood. In vitro, Pg induced significantly higher IL-17 production in anti-CD3 mAb-stimulated monocyte/CD4(+) T-cell co-cultures from patients with PD compared to healthy controls. Our data suggest that periodontal pathogens can activate monocytes, resulting in increased IL-17 production by human CD4(+) T cells, a process that appears enhanced in patients with PD.
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.|Department of Periodontology, Dental Institute, King's College London, London, UK.|Department of Periodontology, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wan-Chien
authors.initials: WC
authors.lastname: Cheng
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.
authors.forename: Saskia D
authors.initials: SD
authors.lastname: van Asten
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.
authors.forename: Lachrissa A
authors.initials: LA
authors.lastname: Burns
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.
authors.forename: Hayley G
authors.initials: HG
authors.lastname: Evans
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.
authors.forename: Gina J
authors.initials: GJ
authors.lastname: Walter
authors.affiliation: Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hashim
authors.affiliation: Department of Periodontology, Dental Institute, King's College London, London, UK.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hughes
authors.affiliation: Division of Immunology, Infection & Inflammatory Disease, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK. leonie.taams@kcl.ac.uk.
authors.forename: Leonie S
authors.initials: LS
authors.lastname: Taams
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005881:Gingiva / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010518:Periodontitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors
keywords: Aggregatibacter actinomycetemcomitans; Interleukin-17; Periodontal disease; Porphyromonas gingivalis; T helper 17 cells