Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition
Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition
复制标题
DOI：
10.4049/jimmunol.177.10.7114
复制
发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Libraty, Daniel H.
中科院分区：
文献类型：
--
作者：
Wang, Jennifer P.;Liu, Ping;Libraty, Daniel H.
TLR7在内体室中感知RNA。TLR7的表达和信号传导已在浆细胞样细胞和髓样树突状细胞、B细胞和T细胞中得到证实。TLR7信号的调控在形成对具有不同细胞趋向性的RNA病毒的免疫应答，以及开发能够促进不道德免疫和细胞介导免疫平衡的佐剂方面发挥关键作用。我们利用两种ssRNA病毒（登革热病毒和流感病毒）的独特特征，描绘了在内体区室中无法识别的病毒rna -人TLR7信号的调节因子。我们的数据表明，TLR7对包膜RNA病毒基因组的识别与病毒融合或从核内体脱壳有关。激活tlr7 -I型IFN产生所需的信号阈值大于激活TLR7-NF-kappa B-IL-8产生所需的信号阈值。病毒RNA的高阶结构似乎是tlr7信号效力的重要决定因素。对病毒RNA-TLR7活性关系的更深入了解将促进制定针对重要人类病毒病原体的干预和疫苗策略的合理方法。
TLR7 senses RNA in endosomal compartments. TLR7 expression and signaling have been demonstrated in plasmacytoid and myeloid dendritic cells, B cells, and T cells. The regulation of TLR7 signaling can play a crucial role in shaping the immune response to RNA viruses with different cellular tropisms, and in developing adjuvants capable of promoting balanced Immoral and cell-mediated immunity. We used unique characteristics of two ssRNA viruses, dengue virus and influenza virus, to delineate factors that regulate viral RNA-human TLR7 signaling beyond recognition in endosomal compartments. Our data show that TLR7 recognition of enveloped RNA virus genomes is linked to virus fusion or uncoating from the endosome. The signaling threshold required to activate TLR7-type I IFN production is greater than that required to activate TLR7-NF-kappa B-IL-8 production. The higher order structure of viral RNA appears to be an important determinant of TLR7-signaling potency. A greater understanding of viral RNA-TLR7 activity relationships will promote rational approaches to interventional and vaccine strategies for important human viral pathogens.