The Role of a Surface Glycoprotein in the Interaction of Aggregatibacter actinomycetemcomitans with Dendritic Cells

Periodontal diseases are a group of prevalent inflammatory diseases affecting the tissues supporting and surrounding the teeth. In periodontal diseases, the inflammatory response of the periodontal tissues is induced by a polymicrobial biofilm formed at or below the gingival margin. Aggregatibacter actinomycetemcomitans, a Gram-negative oral pathogen identified within this biofilm, is a causative agent of both chronic and localized aggressive periodontitis. Dissemination of A. actinomycetemcomitans from the oral cavity also initiates multiple systemic infections, including soft tissues abscesses, pneumonia and endocarditis. The innate immune response is the first line of defense against bacterial infections. Dendritic cells, a group of professional antigen-presenting cells of the innate immune system, express multiple surface C-type lectin receptors for the recognition of glycoproteins associated with bacterial cells. Internalization of the organism by receptor-mediated endocytosis results in phagolysosome formation and degradation of the bacteria for antigen presentation. Surface displayed antigens presented in an MHC complex to antigen-specific T lymphocytes initiate an adaptive immune response. A. actinomycetemcomitans expresses surface structures Extracellular matrix protein adhesin A (EmaA), which extends from the cell envelope, and is composed of three identical glycoproteins. The role of these structures in the interaction of A. actinomycetemcomitans with dendritic cells is understudied. A series of experiments presented here investigated the interaction of A. actinomycetemcomitans with dendritic cells and the role of EmaA in this process. A. actinomycetemcomitans was internalized and found to survive within dendritic cells. The internalization of bacteria was observed to be associated with the presence of EmaA. Fewer emaA mutant bacteria were recovered from dendritic cells when compared with the parent strain. In trans complementation of the emaA mutant strain restored the interactive and survival capability of the bacteria. These data suggest that EmaA mediates the interaction of A. actinomycetemcomitans with dendritic cells. The migration of dendritic cells to draining lymph nodes suggests that the EmaA-mediated internalization and intracellular survival is a potential mechanism for the immune evasion and in vivo dissemination of A. actinomycetemcomitans