Journal
PLOS ONE
Volume 10, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0120498
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Funding
- German Center for Infection Research (DZIF)
- DFG [BA 1618/5-1]
- Behring Rontgen Stiftung [56-0034]
- German National Academic Foundation
- [Transregio-84]
- [SFB1021]
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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.
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