Effect of Aggregatibacter actinomycetemcomitans cytolethal distending toxin on dendritic cells.

摘要

Aggregatibacter actinomycetemcomitans ( Aa) is implicated in localized aggressive periodontitis and strains that secrete a toxin called Cytolethal Distending Toxin (Cdt) are associated with increased severity of disease. Cdt has been shown to target proliferating lymphocytes, resulting in cell cycle arrest and apoptosis. Many lymphocytes responding to the infected periodontium are, however, not actively dividing, raising questions of how Cdt contributes to the disease process. Recent data suggests that Cdt also targets other non-proliferating cells such as macrophages. We therefore believed that Cdt may target antigen presenting cells such as dendritic cells (DCs) and hypothesized that Cdt may influence activation of DCs and facilitate Aa survival within DCs. To address this hypothesis, we examined the interaction of purified Cdt and Aa expressing Cdt on dendritic cells. Our results showed that in the time-frame used in this study, it appears that Aa cannot survive within dendritic cells and get phagocytosed by the DCs. Purified Cdt was also found to be a strong maturation stimulus for in vitro generated dendritic cells, based on flow cytometric analysis of cell surface markers and cytokine response of intoxicated cells, implying that Aa Cdt does not have a direct suppressive affect on DCs.