The role of Tannerella forsythia BspA protein in host-cell interactions
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Periodontal disease (PD) is characterized by chronic inflammation of the tooth supporting tissue and is initiated by pathogen-mediated infection. PD is principally caused by the self-damaging host immune responses involving proinflammatory cytokines. It has been demonstrated that a specific group of oral bacteria play essential roles in PD pathogenesis. In this regard, Tannerella forsythia has recently emerged as an important pathogen. Our long-term goal is to elucidate the mechanisms that underlie the interactions between the organism and the host cells. Despite the fact that T. forsythia has been increasingly recognized as one of the key organisms of the subgingival plaque complex associated with periodontitis, very little is known about the virulence factors or other biochemical or genetic properties of this bacterium. Therefore, it is important to determine which activities or properties of T. forsythia cause or contribute to the pathogenesis. Our main focus in this study was on one of the putative virulence factors of T. forsythia , namely BspA protein. We demonstrated that the BspA protein is an important virulence factor of T. forsythia with multifunctional activities involved in pathogenesis of PD. This is based on our results, which show that BspA activates oral gingival epithelium by activating pattern recognition receptors TLR2/TLR1, important in host innate immunity and inflammation associated with PD. Our investigations identified a specific interaction domain of BspA, the leucine rich repeat domain-1 (LRR-1), involved in TLR2 binding, and further showed that discrete rather than linear epitopes within the LRR-1 domain are likely to be involved in interactions with TLR2/TLR1. During our investigations we also found that BspA expression is required for epithelial cell invasion by T. forsythia , and this might provide the bacterium the ability to evade host immunity. Better understanding of T. forsythia -host interactions will be important in developing intervention strategies against this bacterium that may prevent or reduce PD, and associated diseases and conditions.