Figure 4. Trafficking of pathogens. Localization of pathogens to the endothelium may occur via host immune cells. Oral infection by pathogens such as P. gingivalis leads to considerable tissue damage and stimulates a complex cellular inflammatory lesion that partly characterizes periodontitis. Phagocytic mononuclear cells such as macrophages are responsible for clearance of non-self antigens via phagocytosis and can ingest P. gingivalis at the site of infection in the oral cavity. Upon phagocytosis, it may be possible for some pathogens to resist phagocytic killing and persist within these cells. Without a chemokine gradient to localize to the site of infection, due either to P. gingivalis cysteine protease (gingipain)-mediated cleavage of inflammatory mediators, or to infection-elicited localized chemokine paralysis, infected phagocytes could leave the site of infection and emigrate back to the circulation. These circulating infected macrophages could then interact with immunologically activated endothelial cells at the site of a developing atheroma, first by localizing via a chemotactic gradient (IL-8 and MCP-1), followed by tight adherence to the endothelium via CAMs (green trapezoid). At this point, bacterial antigens or viable bacteria could be released from these cells, and, ultimately, together with elevated levels of circulating lipids such as ox-LDL, result in acceleration of atherosclerosis.