Subgingival Plaque in Periodontal Health Antagonizes at Toll-Like Receptor 4 and Inhibits E-Selectin Expression on Endothelial Cells

WOS: 000367187200003PubMed ID: 26483407The ability of the subgingival microbial community to induce an inappropriate inflammatory response ultimately results in the destruction of bone and gingival tissue. In this study, subgingival plaque samples from both healthy and diseased sites in the same individual were obtained from adults with chronic periodontitis and screened for their ability to either activate Toll-like receptor 2 (TLR2) or TLR4 and to antagonize TLR4-specific activation by agonist, Fusobacterium nucleatum LPS. Subgingival plaque from diseased sites strongly activated TLR4, whereas matched plaque samples obtained from healthy sites were significantly more variable, with some samples displaying strong TLR4 antagonism, while others were strong TLR4 agonists when combined with F. nucleatum LPS. Similar results were observed when TLR4 dependent E-selectin expression by endothelial cells was determined. These results are the first to demonstrate TLR4 antagonism from human plaque samples and demonstrate that healthy but not diseased sites display a wide variation in TLR4 agonist and antagonist behavior. The results have identified a novel characteristic of clinically healthy sites and warrant further study on the contribution of TLR4 antagonism in the progression of a healthy periodontal site to a diseased one.HHS \ NIH \ National Institute of Dental and Craniofacial Research (NIDCR) [R01DE012768, T90DE21984]HHS vertical bar NIH vertical bar National Institute of Dental and Craniofacial Research (NIDCR) provided funding to Richard P. Darveau under grant number R01DE012768. HHS vertical bar NIH vertical bar National Institute of Dental and Craniofacial Research (NIDCR) provided funding to Thao T. To under grant number T90DE21984