TLR9 signals after translocating from the ER to CpG DNA in the lysosome
TLR9 signals after translocating from the ER to CpG DNA in the lysosome
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DOI：
10.1038/ni1028
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发表时间：
2004-02-01
影响因子：
30.5
通讯作者：
Golenbock, DT
中科院分区：
文献类型：
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作者：
Latz, E;Schoenemeyer, A;Golenbock, DT
含有未甲基化CpG二核苷酸的微生物DNA序列可激活Toll样受体9（TLR9）。我们发现TLR9定位于树突状细胞（DCs）和巨噬细胞的内质网（ER）。由于内质网中免疫受体信号传导尚无先例，我们研究了TLR9是如何被激活的。在配体结合研究中我们表明CpG DNA直接与TLR9结合。CpG DNA进入早期内体，随后被转运至管状溶酶体区室。在细胞内CpG DNA移动的同时，TLR9从内质网重新分布到含CpG DNA的结构，这些结构也积聚MyD88。我们的数据表明了一种先前未知的细胞激活机制，涉及从内质网招募TLR9到CpG DNA摄取位点，在此处启动信号转导。
Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is activated. We show that CpG DNA binds directly to TLR9 in ligand-binding studies. CpG DNA moves into early endosomes and is subsequently transported to a tubular lysosomal compartment. Concurrent with the movement of CpG DNA in cells, TLR9 redistributes from the ER to CpG DNA-containing structures, which also accumulate MyD88. Our data indicate a previously unknown mechanism of cellular activation involving the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where signal transduction is initiated.