Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus

被引:178
作者
Hajishengallis, George [1 ]
Tapping, Richard I.
Harokopakis, Evlambia
Nishiyama, So-ichiro
Ratti, Pukar
Schifferle, Robert E.
Lyle, Elizabeth A.
Triantafilou, Martha
Triantafilou, Kathy
Yoshimura, Fuminobu
机构
[1] Univ Louisville, Hlth Sci Ctr, Ctr Oral Hlth & Systemat Dis, Louisville, KY 40292 USA
[2] Univ Louisville, Hlth Sci Ctr, Dept Periodont Endodont, Louisville, KY 40292 USA
[3] Univ Louisville, Hlth Sci Ctr, Dept Orthodont Pedodont, Louisville, KY 40292 USA
[4] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA
[5] Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Nagoya, Aichi 4648650, Japan
[6] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, New Orleans, LA 70119 USA
[7] Univ Buffalo, Dept Oral Biol, Buffalo, NY 14214 USA
[8] Univ Sussex, Sch Life Sci, Infect & Immun Grp, Brighton BN1 9QG, E Sussex, England
基金
英国惠康基金;
关键词
D O I
10.1111/j.1462-5822.2006.00730.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 [细胞生物学]; 090102 [作物遗传育种];
摘要
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.
引用
收藏
页码:1557 / 1570
页数:14
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