Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus.
The lipopolysaccharide (LPS) and fimbriae of Porphyromonas gingivalis play important roles in periodontal inflammation and pathogenesis. We investigated fimbriae and LPS from several P. gingivalis strains in terms of relative dependence on Toll-like receptor (TLR) signalling partners or accessory pattern-recognition molecules mediating ligand transfer to TLRs, and determined induced assembly of receptor complexes in lipid rafts. Fimbriae could utilize TLR1 or TLR6 for cooperative TLR2-dependent activation of transfected cell lines, in contrast to LPS and a mutant version of fimbriae which displayed preference for TLR1. Whether used to activate human cell lines or mouse macrophages, fimbriae exhibited strong dependence on membrane-expressed CD14 (mCD14), which could not be substituted for by soluble CD14 (sCD14). In contrast, sCD14 efficiently substituted for mCD14 in LPS-induced cellular activation. LPS-binding protein was more important for LPS- than for fimbria-induced cell activation, whereas the converse was true for CD11b/CD18. Cell activation by LPS or fimbriae required lipid raft function and formation of heterotypic receptor complexes (TLR1-2/CD14/CD11b/CD18), although wild-type fimbriae additionally recruited TLR6. In summary, TLR2 activation by P. gingivalis LPS or fimbriae involves differential dependence on accessory signalling or ligand-binding receptors, which may differentially influence innate immune responses.
Hajishengallis
George
G
Center for Oral Health and Systemic Disease and Department of Periodontics/Endodontics, University of Louisville Health Sciences Center, Louisville, KY 40292, USA. g0haji01@louisville.edu
Tapping
Richard I
RI
Harokopakis
Evlambia
E
Nishiyama
So-ichiro
S
Ratti
Pukar
P
Schifferle
Robert E
RE
Lyle
Elizabeth A
EA
Triantafilou
Martha
M
Triantafilou
Kathy
K
Yoshimura
Fuminobu
F
D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D018929:Cell Culture Techniques; D002460:Cell Line; D010861:Fimbriae, Bacterial / Q000276:immunology*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007113:Immunity, Innate; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D021962:Membrane Microdomains / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000166:cytology / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000276:immunology; D014162:Transfection; D047392:beta-Cyclodextrins / Q000494:pharmacology
D039481:CD11b Antigen; D018821:CD18 Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin