Spatiotemporal regulation of nucleic acid uptake and signaling

点击翻译按钮获取中文摘要

Endosomal Toll-like receptor (TLR) 3 serves as a sensor of viral infection and sterile tissue necrosis and activates innate and adaptive immunity. Although TLR3 recognizes double-stranded (ds) RNA, little is known about structural features of virus- or host-derived RNAs that activate TLR3 in infection/inflammatory states. In this study, we demonstrate that single-stranded RNAs harboring stable incomplete stem structures are potent TLR3 agonists. Like poly(I:C), a synthetic dsRNA, these structured RNAs were internalized into cells via raftlin-mediated endocytosis and activated TLR3. Based on the ligand recognition mode of TLR3 and uptake mechanism of extracellular nucleic acids, we have generated novel TLR3 ligand that activates endosomal TLR3 but not cytoplasmic RNA sensors.