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PLoS One. 2015 Mar 18;10(3):e0120498. doi: 10.1371/journal.pone.0120498. eCollection 2015.

A single naturally occurring 2'-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand.

Author information

1
Institut für Immunologie, Philipps-Universität Marburg, BMFZ, Marburg, Germany.
2
Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, München, Germany.

Abstract

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-α 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.

PMID:
25785446
PMCID:
PMC4364935
DOI:
10.1371/journal.pone.0120498
[Indexed for MEDLINE]
Free PMC Article

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