Kanaya S, Nemoto E, Ogawa T, Shimauchi H
Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
J Periodontal Res. 2009 Aug;44(4):543-9. doi: 10.1111/j.1600-0765.2008.01149.x. Epub 2009 Oct 7.
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.
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.
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.
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.
树突状细胞（DCs）在T细胞激活以及塑造免疫反应过程中发挥关键作用。我们之前报道过，牙龈卟啉单胞菌脂多糖（Pg LPS）可诱导产生具有较弱免疫刺激活性的CD14(+)CD16(+) DC亚群。相比之下，大肠杆菌脂多糖（Ec LPS）可诱导产生具有强免疫刺激活性的完全成熟的DCs。由于Pg LPS以及Pg菌毛已被证实可作为Toll样受体（TLR）2配体发挥作用，我们推测细菌抗原对TLR的利用可能对DC成熟至关重要。
我们将Pg菌毛与一种TLR2配体肽聚糖以及一种TLR4配体Ec LPS进行比较，研究了Pg菌毛对人外周血DCs表型和功能的影响。
流式细胞术显示，Pg菌毛和肽聚糖可诱导外周血DCs（CD14(-)CD16(-)）表达CD14和CD16，但Ec LPS无此作用。抗TLR2单克隆抗体可消除这种诱导作用，但抗TLR4抗体则无影响。与用Ec LPS刺激的DCs相比，用Pg菌毛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的产生也较少，且在激活后表达和分泌的调节正常T细胞表达和分泌因子（RANTES）也较弱。
这些结果表明，不同的TLR利用会影响成熟DC的表型和功能，因此对于病原体免疫调节至关重要。
