Deoxyguanosine is a TLR7 agonist
Deoxyguanosine is a TLR7 agonist
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DOI：
10.1002/eji.201948151
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发表时间：
2019-11-14
影响因子：
5.4
通讯作者：
Rehwinkel, Jan
中科院分区：
文献类型：
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作者：
Davenne, Tamara;Bridgeman, Anne;Rehwinkel, Jan
Toll样受体7（TLR 7）是单链RNA（ssRNA）的先天性免疫传感器。最近的结构分析显示，TLR 7有一个额外的核苷如鸟苷的结合位点，并在鸟苷和ssRNA结合时被激活。核苷结合位点还容纳咪唑并喹啉衍生物，如R848，其在ssRNA不存在的情况下激活TLR 7。在这里，我们报告说，脱氧鸟苷（dG）触发细胞因子的产生在小鼠骨髓来源的巨噬细胞和浆细胞样树突状细胞，以及在人外周血单核细胞，包括I型干扰素和促炎因子，如TNF和IL-6。dG的这种信号传导活性依赖于TLR 7及其接头MyD 88，并且不需要通过I型干扰素受体进行扩增。DG触发的细胞因子产生需要内体成熟，但不依赖于RNA的同时提供。我们的结论是，dG通过TLR 7诱导炎症反应，并提出dG是一种RNA非依赖性TLR 7激动剂。
Toll-like receptor 7 (TLR7) is an innate immune sensor for single-strand RNA (ssRNA). Recent structural analysis revealed that TLR7 has an additional binding site for nucleosides such as guanosine, and is activated when both guanosine and ssRNA bind. The nucleoside binding site also accommodates imidazoquinoline derivatives such as R848, which activate TLR7 in the absence of ssRNA. Here, we report that deoxyguanosine (dG) triggered cytokine production in murine bone marrow derived macrophages and plasmacytoid dendritic cells, as well as in human peripheral blood mononuclear cells, including type I interferons and pro-inflammatory factors such as TNF and IL-6. This signalling activity of dG was dependent on TLR7 and its adaptor MyD88 and did not require amplification via the type I interferon receptor. dG-triggered cytokine production required endosomal maturation but did not depend on the concurrent provision of RNA. We conclude that dG induces an inflammatory response through TLR7 and propose that dG is an RNA-independent TLR7 agonist.