Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis

Abstract

In periodontitis, a common chronic inflammatory condition, gram negative-rich bacterial biofilms trigger, in susceptible individuals, perpetuating inflammation that results in extensive tissue damage of tooth supporting structures. To delineate immune cell-dependent mechanisms whereby bacterial challenge drives persistent destructive inflammation in periodontitis and other inflammatory diseases, we studied involved tissues ex vivo and investigated host cell responses to the periodontal pathogen P. gingivalis, in vitro. Diseased lesions were populated by abundant Th17 cells, linked to infection, chronic inflammation/autoimmunity and tissue pathology. In vitro, P. gingivalis, particularly the more virulent strain W83, stimulated myeloid antigen presenting cells (APC) to drive Th17 polarization. Supernatants from myeloid APC exposed to P. gingivalis were capable of enhancing Th17 but not Th1 polarization. P. gingivalis favored the generation of Th17 responses by stimulating the production of Th17 related cytokines IL-1β, IL-6 and IL-23, but not Th1 related IL-12. By inducing NFκB activation, P. gingivalis promoted IL-1β, IL-6 and IL-12p40 production, but not IRF-3 phosphorylation, connected to generation of the IL-12p35 chain, ultimately restricting formation of the intact IL-12 molecule. Promotion of Th17 lineage responses was also aided by P. gingivalis proteases, which appeared to differentially degrade pivotal cytokines. In this regard, IL-12 was largely degraded by P. gingivalis, whereas IL-1β was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies.

Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2- and IL-1–Driven Th17 Response

“…This is in line with Th17 induction by P. gingivalis in humans and a previous study showing that intramucosal inoculation of P. gingivalis in naive mice can induce a kinin-dependent Th17 phenotype (34,37,38). In addition, increased mRNA expression of T cell-related transcription factors has been shown in submandibular lymph nodes of mice upon coinduction of pristaneinduced arthritis and Agregatibacter actinomycetemcomitansinduced PD (39).…”

Porphyromonas gingivalisand adverse pregnancy outcome

“…More recently, it has been demonstrated that P. gingivalis favors T helper cell polarization to a TH17 profile with generation of TH17-related cytokines [30] and that the P. gingivalis induced T cell differentiation shift is highly specific towards a TH17 cell phenotype in an IL-6 dependent manner [31]. Moreover, a periodontitis rat model study showed a variable sitespecific TH17/Treg cell ratio in the oral tissues but detected a TH17 cell increase with a relative Treg cell decrease in peripheral blood, which was proposed to potentially impact development of systemic inflammatory diseases [32].…”

Functional Imbalance between Th17, Th1, and Treg Cells in A. actinomyctemcomitans -Accelerated Atherosclerosis

“…The increase of Th17 cells in chronic periodontal patients and by Porphyromonas gingivalis exposure to peripheral blood mononuclear cells in vitro were also recognized (13,14).…”