Mechanisms of TLR9 activation
Mechanisms of TLR9 activation
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DOI：
10.1179/096805104225006525
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发表时间：
2004-01-01
期刊：
影响因子：
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通讯作者：
Golenbock, DT
中科院分区：
文献类型：
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作者：
Latz, E;Visintin, A;Golenbock, DT
细菌或病毒DNA中的非甲基化CpG基序被TLR 9识别为外来物。微生物DNA或基于这些基序的合成寡核苷酸对TLR 9的激活导致先天免疫应答的诱导。我们比较了TLR 9和TLR 4的荧光版本的亚细胞定位，发现TLR 9在内质网中表达，而TLR 4在质膜上表达。观察到标记的细菌DNA或CpG-DNA运输到人pDC中的管状溶酶体区室。在受刺激的细胞中，TLR 9易位至内体中含有CpG-DNA或微生物DNA的结构，其中TLR 9结合DNA并启动信号传导。
Non-methylated CpG-motifs in bacterial or viral DNA are recognized by TLR9 as foreign. The activation of TLR9 by microbial DNA or synthetic oligonucleotides based on these motifs leads to the induction of innate immune responses. We have compared the subcellular localization of fluorescent versions of TLR9 and TLR4 and found that TLR9 is expressed in the endoplasmic reticulum while TLR4 is expressed on the plasma membrane. Fluorescently tagged bacterial DNA or CpG-DNA was observed to traffic to a tubular lysosomal compartment in human pDCs. In stimulated cells, TLR9 translocated to CpG-DNA or microbial DNA containing structures in the endosome, where TLR9 binds to DNA and initiates signaling.