Takeshita F, Leifer C A, Gursel I, Ishii K J, Takeshita S, Gursel M, Klinman D M
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 2001 Oct 1;167(7):3555-8. doi: 10.4049/jimmunol.167.7.3555.
Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are stimulated by CpG motifs that are active in primates but not rodents, suggesting that evolutionary divergence between TLR9 molecules underlies species-specific differences in the recognition of bacterial DNA. These findings indicate that hTLR9 plays a critical role in the CpG DNA-mediated activation of human cells.
细菌DNA中存在的未甲基化CpG基序可刺激快速而强烈的先天性免疫反应。识别CpG DNA的人类细胞系和外周血单核细胞表达膜结合型人类 Toll 样受体9（hTLR9）。对CpG DNA无反应的细胞在转染hTLR9后会变得有反应。hTLR9的表达显著增加了CpG（而非对照）DNA进入内吞小泡的摄取。细胞受到刺激后，hTLR9和CpG DNA存在于相同的内吞小泡中。表达hTLR9的细胞受到在灵长类动物中具有活性但在啮齿动物中无活性的CpG基序的刺激，这表明TLR9分子之间的进化差异是细菌DNA识别中物种特异性差异的基础。这些发现表明hTLR9在CpG DNA介导的人类细胞激活中起关键作用。
