Treponema Denticola Activates NF-κB Pathway via Toll-like Receptor 2.

Abstract

Treponema denticola is frequently isolated together with Porphyromonas gingivalis from the lesions seen in cases of chronic periodontitis and is considered a major pathogen of this disease. It has several virulence factors, including a major surface protein (Msp) and a major surface protease, dentilisin. The effect of these virulence factors on the host immune response remains to be elucidated, however. Toll-like receptors (TLRs) in the host can recognize pathogen-associated molecular patterns. Bacteria stimulate TLRs and activate the pro-inflammatory nuclear factor-kappa B pathway. Therefore, the aim of this study was to investigate the effect of T. denticola on TLR pathways. Toll-like receptor 4 and TLR2 reporter cell lines, which secrete alkaline phosphatase in response to TLR signals, were infected with the T. denticola wild type, an Msp-deficient mutant, a dentilisin-deficient mutant, or their extracts obtained via sonication. Signals from TLR2 or TLR4 cells were evaluated by alkaline phosphatase activity. Toll-like receptor 2 signals were detected in all T. denticola strains and sonication extracts, while no TLR4 signal was detected. Infection with the dentilisin-deficient mutant induced the strongest TLR2 signal among the strains. Sonication extracts of the wild type and Msp-deficient mutant showed the same level of TLR2 signaling. The TLR2 signal in the sonication extracts from the wild type was inhibited by Sparstolonin B, an antagonist of TLR2, in a dose-dependent manner. These results indicate that T. denticola is recognized by epithelial cells mainly via TLR2. The outer sheath structure may conceal potential ligands for TLR2.