A Single Naturally Occurring 2 '-O-Methylation Converts a TLR7-and TLR8-Activating RNA into a TLR8-Specific Ligand

作者：Jung Stephanie; von Thuelen Tina; Laukemper Viktoria; Pigisch Stephanie; Hangel Doris; Wagner Hermann; Kaufmann Andreas; Bauer Stefan^*

来源：PLos One, 2015, 10(3): e0120498.

DOI：10.1371/journal.pone.0120498

TLR7 and TLR8 recognize RNA from pathogens and lead to subsequent immune stimulation. Here we demonstrate that a single naturally occurring 2'-O-methylation within a synthetic 18s rRNA derived RNA sequence prevents IFN-alpha production, however secretion of proinflammatory cytokines such as IL-6 is not impaired. By analysing TLR-deficient plasmacytoid dendritic cells and performing HEK293 genetic complementation assays we could demonstrate that the single 2'-O-methylation containing RNA still activated TLR8 but not TLR7. Therefore this specific 2'-O-ribose methylation in rRNA converts a TLR7 / TLR8 ligand to an exclusively TLR8-specific ligand. Interestingly, other modifications at this position such as 2'-O-deoxy or 2'-fluoro had no strong modulating effect on TLR7 or TLR8 activation suggesting an important role of 2'-O-methylation for shaping differential TLR7 or TLR8 activation.

• 出版日期2015-3-18
• 单位河北医科大学