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.