Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

Front Immunol. 2018 Mar 16;9:516. doi: 10.3389/fimmu.2018.00516. eCollection 2018.

Abstract

Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.

Keywords: IFN; TLR10; dsRNA; interferon regulatory factor; ligand sequestration; myeloid differentiation primary response gene 88; nucleotide-sensing receptor; toll-like receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endosomes / metabolism
  • Humans
  • Interferons / metabolism*
  • RNA, Double-Stranded / metabolism*
  • Signal Transduction
  • THP-1 Cells
  • Toll-Like Receptor 10 / metabolism*
  • Toll-Like Receptor 3 / metabolism*

Substances

  • RNA, Double-Stranded
  • TLR10 protein, human
  • TLR3 protein, human
  • Toll-Like Receptor 10
  • Toll-Like Receptor 3
  • Interferons