Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus
Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus
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DOI：
10.1111/j.1462-5822.2006.00730.x
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Yoshimura, Fuminobu
中科院分区：
文献类型：
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作者：
Hajishengallis, George;Tapping, Richard I.;Yoshimura, Fuminobu
牙龈卟啉单胞菌的脂多糖（LPS）和菌毛在牙周炎的发生和发展中起重要作用。我们研究了菌毛和LPS从几个牙龈卟啉单胞菌菌株的相对依赖性Toll样受体（TLR）的信号合作伙伴或辅助模式识别分子介导的配体转移到TLR，并确定诱导组装的受体复合物的脂筏。菌毛可以利用TLR 1或TLR 6的合作TLR 2依赖性激活转染的细胞系，在相反的LPS和突变体版本的菌毛显示偏好TLR 1。无论是用于激活人细胞系还是小鼠巨噬细胞，菌毛都表现出对膜表达的CD 14（mCD 14）的强烈依赖性，而可溶性CD 14（sCD 14）不能替代mCD 14。相反，sCD 14在LPS诱导的细胞活化中有效地取代了mCD 14。LPS结合蛋白对LPS诱导的细胞活化比菌毛诱导的细胞活化更重要，而CD 11b/CD 18则相反。LPS或菌毛的细胞活化需要脂筏功能和异型受体复合物（TLR 1 -2/CD 14/CD 11b/CD 18）的形成，尽管野生型菌毛额外招募TLR 6。总之，由牙龈卟啉单胞菌LPS或菌毛激活的TLR 2涉及对辅助信号传导或配体结合受体的差异依赖性，这可能差异地影响先天免疫应答。
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.