Modulation of the host response to commensal oral biofilm by the periodontal pathogen Tannerella forsythia

There is emerging evidence that periodontal pathogens do not only elicit a host response to themselves; they might also influence the reactivity of the immune system to other pathogens and even commensals. This capability was investigated for P. gingivalis but not for the other members of the “red complex” of pathogens, particularly, T. forsythia. Previous studies by our groups have shown that T. forsythia cells, LPS and outer membrane vesicles activate inflammatory responses in different host cells such as macrophages, epithelial cells, gingival fibroblasts, and periodontal ligament cells. However, it is not known to date if and how T. forsythia modulates the host response and host susceptibility to the oral commensal microflora. We hypothesize that T. forsythia has the potential to manipulate the response of host immune cells to commensal oral microorganisms as present in dental plaque. This might be achieved by a direct effect of T. forsythia on the host immune system or by alteration of the pathogenicity of the oral biofilm. Within the frame of the present project, the following specific questions will be addressed: (1) Influence of the presence of T. forsythia on the inflammatory response and barrier properties of oral epithelial cells to the healthy (commensal) oral biofilm. (2) Effect of T. forsythia-containing healthy oral biofilm on the physiological properties and transepithelial migration of neutrophils and macrophages, which are primarily involved in the control of oral biofilm growth. (3) Effect of T. forsythia incorporated in healthy oral biofilm on gingival fibroblasts and their ability to modulate the immune response. To answer these questions, in vitro co-culture models of various host cells and a simplified multispecies healthy oral biofilm will be established and compared to the same stimuli plus the periodontal pathogen T. forsythia. The effects of T. forsythia will be compared to those triggered by P. gingivalis. This study will allow answering the question about a possible modulation of the commensal biofilm-host interaction by the periodontal pathogen T. forsythia and its potential role in the initiation and development of periodontitis.