King's College London

Research portal

Periodontitis-associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14+ monocytes leading to enhanced Th17/IL-17 responses

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2211-2221
JournalEuropean Journal of Immunology
Volume46
Issue number9
Early online date23 Jun 2016
DOIs
Accepted/In press17 Jun 2016
E-pub ahead of print23 Jun 2016
PublishedSep 2016

Documents

King's Authors

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.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454