Interaction of Actinobacillus actinomycetemcomitans with antigen-presenting cells (dendritic cells)

Abstract

It becomes clear that the interaction between dendritic cells (DCs) and pathogens is a significant factor in determining the effectiveness of the immune response and the outcome of disease. Periodontitis is a chronic bacterial infection which is characterized by a destructive inflammatory process affecting periodontal tissues and bone. The immunopathogenesis of the disease involves the interaction between host defense mechanisms and Gram negative bacteria and their products such as lipopolysaccharide (LPS) in dental plaque. We therefore attempted to investigate the interaction of LPS derived from Actinobacillus actinomycetemcomitans, one of the key periodontal pathogens, with dendritic cells. Immature dendritic cells were generated from CD14+ monocytes culturing in medium supplemented with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. These immature DCs when stimulated with A. actinomycetemcomitans LPS in vitro for 24 h. led to cell maturation associated with the enhanced expression of co-stimulatory molecules (CD40 and CD80), a maturation marker (CD83) and human leukocyte antigen (HLA)-DR. A. actinomycetemcomitans LPS at 1,000 ng/ml induced minimally production of cytokines. Moderate amount of tumor necrosis factor-a was consistently observed, however, we could not detect any IL-12 production. In mixed leukocyte reaction, A. actinomycetemcomitans LPS treated DCs promoted T-helper 1 (Th1) response as indicated by predominant production of interferon-g but not IL-4 and IL-10 by allogeneic T cells. In conclusion, our study demonstrated that we were able to generate DCs from flow cytometrically sorted CD14+ monocytes in culture with GM-CSF and IL-4. The immature DCs became mature when stimulated with A. actinomycetemcomitans LPS and capable to drive Th1 response. However, it is too early to draw any conclusion concerning the effect of A. actinomycetemcomitans on DC induced Th response. How this Th development associated with the pathogenesis of periodontitis would require further investigation.