Oral Polymicrobial Community Activation of Toll-like Receptor 4

Thesis (Ph.D.)--University of Washington, 2015Chronic periodontitis is characterized by not only the dysbiotic polymicrobial community which lies below the gumline, but also how this community triggers overwhelming and persistent inflammatory responses from the host innate immune system. In this work, we describe how the subgingival microbial community as a whole engages a major innate immune receptor, Toll-like receptor 4 (TLR4), in either health or disease states. The plaque polymicrobial community in disease potently activates TLR4; however, subgingival plaque collected from healthy sites not only suppress NF-kB signaling through TLR4 suppression, but also dampens expression of neutrophil recruitment molecule, E-selectin, on the surface of endothelial cells. To our knowledge, this is the first report of any clinical patient sample of a polymicrobial community acting on TLR4 in an antagonistic manner. Additionally, we demonstrate how the metabolic relationship between two bacteria, highly associated together in disease- F. nucleatum and P. gingivalis- synergistically work together to promote a pro-inflammatory state through TLR4 activation. This phenomena is not observed when F. nucleatum is grown in co-culture with S. gordonii, a relationship more associated with a more healthy periodontal status. Taken together, our work elucidates the role of polymicrobial communities on TLR4 activation in health and disease