Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides
Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides
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DOI：
10.4049/jimmunol.168.9.4531
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发表时间：
2002-05-01
影响因子：
4.4
通讯作者：
Hartmann, G
中科院分区：
文献类型：
--
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
Toll样受体(TLR)9对免疫刺激CpG基序的识别至关重要，但可能与其他TLRs协同作用。我们用实时定量聚合酶链式反应分析了高纯度的人PBMC亚群中TLR1-10mRNA的表达，并测定了这些亚群对CpG寡脱氧核苷酸(ODN)的敏感性。TLR1和TLR6在所检测的所有细胞类型中均有表达。TLR10高表达于B细胞，弱表达于浆细胞样树突状细胞(PDC)。单核细胞高表达TLR2是其特征。PDC和B细胞表达明显的TLR7和TLR9，对CpG ODN直接敏感。在CpG ODN刺激的PDC和B细胞中，TLR9的表达迅速下降，而TLR7在PDC中表达上调，而在B细胞中表达降低。在单核细胞、NK细胞和T细胞中，TLR7缺失。尽管TLR9低表达，但单核细胞、NK细胞和T细胞在没有PDC的情况下对CpG ODN没有反应，但在PDC的存在下被激活。总之，我们的研究提供了证据，证明PDC和B细胞，而不是单核细胞，NK细胞或T细胞是CpG ODN在外周血中的主要靶点。TLR1-10在人PBMC细胞亚群中的特征表达模式与TLR9在PDC和B细胞中识别CpG ODN所必需的概念是一致的。此外，CpG ODN选择性调节PDC和B细胞TLR7的表达表明TLR7是一个候选TLR，可能参与调控CpG基序的识别。
The Toll-like receptor (TLR)9 is critical for the recognition of immunostimulatory CpG motifs but may cooperate with other TLRs. We analyzed TLR1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of human PBMC and determined the sensitivity of these subsets to CpG oligodeoxynucleotides (ODN). TLR1 and TLR6 were expressed in all cell types examined. TLR10 was highly expressed in B cells and weakly expressed in plasmacytoid dendritic cells (PDC). High expression of TLR2 was characteristic for monocytes. PDC and B cells expressed marked levels of TLR7 and TLR9 and were directly sensitive to CpG ODN. In CpG ODN-stimulated PDC and B cells, TLR9 expression rapidly decreased, as opposed to TLR7, which was up-regulated in PDC and decreased in B cells. In monocytes, NK cells, and T cells, TLR7 was absent. Despite low expression of TLR9, monocytes, NK cells, and T cells did not respond to CpG ODN in the absence of PDC but were activated in the presence of PDC. In conclusion, our studies provide evidence that PDC and B cells, but not monocytes, NK cells, or T cells, are primary targets of CpG ODN in peripheral blood. The characteristic expression pattern of TLR1-10 in cellular subsets of human PBMC is consistent with the concept that TLR9 is essential in the recognition of CpG ODN in PDC and B cells. In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs.