Involvement of Toll-like receptors 2 and 4 in the innate immune response to Treponema denticola and its outer sheath components.
Treponema denticola is considered an important oral pathogen in the development and progression of periodontal diseases. In the present study, the mechanisms of recognition and activation of murine macrophages by T. denticola and its major outer sheath protein (MSP) and lipooligosaccharide (LOS or glycolipid) were investigated. T. denticola cells and the MSP induced innate immune responses through TLR2-MyD88, whereas LOS induced a macrophage response through TLR4-MyD88. The presence of gamma interferon (IFN-gamma), or of high numbers of T. denticola, circumvented the requirement for TLR2 for the macrophage response to T. denticola, although the response was still dependent on MyD88. In contrast, synergy with IFN-gamma did not alter the TLR dependence of the response to the T. denticola surface components LOS and MSP, despite enhanced sensitivity. These data suggest that although there is flexibility in the requirements for recognition of T. denticola cells (TLR2 dependent or independent), MyD88 is a requirement for the downstream signaling events that lead to inflammation. We also demonstrate that both outer sheath molecules LOS and MSP induce macrophage tolerance to further stimulation with enterobacterial lipopolysaccharide. Tolerance induced by T. denticola components during mixed infections may represent a general mechanism through which bacteria evade clearance.
Nussbaum
Gabriel
G
Institute of Dental Sciences, Faculty of Dental Medicine, Hadassah and Hebrew University Medical Center, Jerusalem, Israel. gabrieln@ekmd.huji.ac.il
Ben-Adi
Shimon
S
Genzler
Tamar
T
Sela
Michael
M
Rosen
Graciela
G
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D018272:Porins / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D048373:Treponema denticola / Q000276:immunology*
D001426:Bacterial Proteins; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018272:Porins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C023023:lipid-linked oligosaccharides; C099361:major outer sheath protein, Treponema; D007371:Interferon-gamma