Porphyromonas gingivalis Mediated Periodontal Disease and Atherosclerosis:Disparate Diseases with Commonalities in Pathogenesis Through TLRs

Frank   C.   Gibson III; Caroline   A.   Genco

Abstract

Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy.

Keywords: Atherosclerosis, Inflammation, Periodontal disease, P. gingivalis, TLR2, TLR4, Endothelial cells, Macrophages