Treponemal glycoconjugate inhibits Toll-like receptor ligand-induced cell activation by blocking LPS-binding protein and CD14 functions.
Spirochetes are well-known as causative agents of various chronic infectious diseases. Glycolipids of small-sized Treponema spirochetes have been shown to exhibit immunostimulating activities. In this study, we found that a glycoconjugate preparation obtained from Treponema medium (Tm-Gp), an intermediate-sized oral Treponema seen in subgingival plaque from patients with chronic periodontal diseases, diminished the LPS-induced activation of a human monocytic cell line, while TNF-alpha-induced activation was unaffected. NF-kappaB activation in Ba/F3 cells expressing murine Toll-like receptor (TLR) 4 and MD-2 was inhibited by Tm-Gp in a CD14/LPS-binding protein (LBP)-dependent manner when stimulated with LPS or its active center lipid A but not when stimulated with Taxol. Tm-Gp blocked the binding of LPS to immobilized CD14 and LBP and inhibited nitric oxide (NO) production by a murine Mphi cell line following stimulation with peptidoglycan and LPS in the presence of FBS, while NO production in response poly (I:C) RNA or CpG DNA remained unaffected. The inhibitory effects of Tm-Gp seem to be attributable to the lipophilic portion of the glycoconjugate. These results indicate that T. medium contains a glycoconjugate possessing an inhibitory effect on TLR-mediated cell activation through interaction with LBP and CD14.
Department of Oral Microbiology, Asahi University School of Dentistry, Gifu, Japan.
Yasuyuki
Y
Asai
Masahito
M
Hashimoto
Tomohiko
T
Ogawa
D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D006001:Glycoconjugates / Q000276:immunology*; D006737:Horseshoe Crabs / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014208:Treponema / Q000276:immunology*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D006001:Glycoconjugates; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein; C495345:TLR4 protein, human; C025357:endotoxin binding proteins