Impacts of Nucleoside Modification on RNA-Mediated Activation of Toll-Like Receptors

DNA and RNA stimulate the mammalian innate immune system by triggering a variety of nucleic acid-responsive sensors including Toll-like receptors (TLRs). TLR9 present in the endosomal compartments of immune cells responds to DNA. TLR3 is activated by dsRNA, while TLR7 and human TLR8 signal when exposed to single-stranded RNA. Most DNA and RNA from natural sources contain modified nucleosides. In eukaryotes, modification of DNA is limited to 5-methylcytidine of CpG motifs; whereas in RNA more than 100 different types of modified nucleosides have been identified.