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J Autoimmun 2012 Dec;39(4):294-303

Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis.

Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, Osorio M, Wahl SM


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 Porphyromonas 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-1beta, IL-6 and IL-23, but not Th1 related IL-12. By inducing NFkappaB activation, P. gingivalis promoted IL-1beta, IL-6 and IL-12p40 production, but not IRF3 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-1beta was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies.

Category: Journal Article
PubMed ID: #22560973 DOI: 10.1016/j.jaut.2012.03.003
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2013-02-14