Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease

Abstract

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

Keywords: DC-SIGN; Porphyromonas gingivalis; atherosclerosis; dendritic cells; periodontitis.

Figures

Fig. 1

Schematic representation of how P. gingivalis-laden dendritic cells may promote atheroma formation and maturation. (A) Representation of the oral lymphoid foci, its organized inflammatory infiltrate. The left panel depicts the healthy oral biofilm in the gingival crevice, comprised predominantly of Gram-positive bacteria (green dots). Healthy gingival tissue is infiltrated with numerous Langerhans cells in the epithelium, with sparse dermal dendritic cells in the lamina propria. As disease progresses, the oral biofilm changes to a predominantly Gram-negative subgingival flora (red dots). In response, a dramatic loss (efflux) of Langerhans cells occurs from the epithelium toward the lamina propria. Also observed is an influx of myeloid-derived DC-SIGN+ dermal dendritic cells (DCs) into the lamina propria. Present are neutrophils, macrophages (mɸ), B-cells, and CD4+ and CD8+ T-cells. The DCs form immune conjugates with CD4+ T-cells and also mobilize toward the vasculature. (B) Hypothetical model in periodontitis, showing mobilization of P. gingivalis-laden DC-SIGN+ myeloid DCs (mDCs) in the gingival lamina propria. These mDCs undergo reverse transmigration through the vascular endothelium. Once in the circulation, mDCs carrying P. gingivalis attach to endothelial integrins via DC-SIGN and, after rolling adhesion, undergo diapedesis between endothelial cells. As the atheroma continues to mature and DCs contribute to the foam cells and release MMP-9, the atheroma becomes highly unstable and, eventually, thrombus formation occurs.