Porphyromonas gingivalis fimbriae induce unique dendritic cell subsets via Toll-like receptor 2
Porphyromonas gingivalis fimbriae induce unique dendritic cell subsets via Toll-like receptor 2
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DOI：
10.1111/j.1600-0765.2008.01149.x
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发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Shimauchi, H.
中科院分区：
文献类型：
--
作者：
Kanaya, S.;Nemoto, E.;Shimauchi, H.
背景与目的：树突状细胞（dc）在T细胞的激活以及形成免疫反应中起着关键作用。我们之前报道过牙龈卟啉单胞菌脂多糖（Pg LPS）诱导CD14(+)CD16(+) DC亚群具有弱的免疫刺激活性。相比之下，大肠杆菌LPS （Ec LPS）诱导完全成熟的树突状细胞具有较强的免疫刺激活性。由于Pg脂多糖和Pg菌毛已被证明可以作为toll样受体（TLR） 2配体，我们推测细菌抗原的TLR使用可能对DC成熟至关重要。材料与方法：通过与TLR2配体肽聚糖和TLR4配体Ec LPS的比较，我们研究了Pg菌膜对人外周血dc表型和功能的影响。结果：流式细胞术显示Pg菌毛和肽聚糖诱导外周血dc细胞CD14和CD16的表达（CD14(-)），而Ec LPS不诱导CD14和CD16的表达（CD14(-)）。抗TLR2的单克隆抗体消除了这种诱导作用，但抗TLR4的抗体没有作用。与Ec LPS刺激的树突状细胞相比，Pg刺激的树突状细胞诱导同种异体T细胞增殖的能力较弱，白细胞介素-8的产生较弱，激活后正常T细胞表达和分泌（RANTES）受到调节。结论：不同TLR用量影响成熟DC的表型和功能，对调节DC对病原菌的免疫具有重要作用。
Backgound and Objective:Dendritic cells (DCs) play a critical role in the activation of T cells as well as in shaping immune responses. We have reported previously that Porphyromonas gingivalis lipopolysaccharides (Pg LPS) induced a CD14(+)CD16(+) DC subset with a weak immuno-stimulatory activity. In contrast, Escherichia coli LPS (Ec LPS) induced fully matured DCs with strong immunostimulatory activities. Since Pg LPS as well as Pg fimbriae have been indicated to work as Toll-like receptor (TLR) 2 ligands, we speculate that the TLR usage of bacterial antigens may be critical for DC maturation.Material and Methods:We investigated the effect of Pg fimbriae on the phenotype and function of human peripheral blood DCs in comparison with a TLR2 ligand, peptidoglycan, and a TLR4 ligand, Ec LPS.Results:Flow cytometry revealed that Pg fimbriae and peptidoglycan but not Ec LPS induced CD14 and CD16 expression on peripheral blood DCs (CD14(-)CD16(-)). A monoclonal antibody against TLR2 abrogated this induction, but an antibody against TLR4 had no effect. Dendritic cells stimulated with Pg fimbriae had a weaker capability to induce allogenic T cell proliferation and exhibited a weaker production of interleukin-8 and regulated upon activation, normal T cell expressed and secreted (RANTES) than DCs stimulated with Ec LPS.Conclusion:These results indicate that different TLR usage affects mature DC phenotype and function and is thus crucial to the regulation of immunity to the pathogen.