Self-priming determines high type I IFN production by plasmacytoid dendritic cells

Eur J Immunol. 2014 Mar;44(3):807-818. doi: 10.1002/eji.201343806. Epub 2014 Jan 16.


Plasmacytoid dendritic cells (pDCs) are responsible for the robust and immediate production of type I IFNs during viral infection. pDCs employ TLR7 and TLR9 to detect RNA and CpG motifs present in microbial genomes. CpG-A was the first synthetic stimulus available that induced large amounts of IFN-α (type I IFN) in pDCs. CpG-B, however, only weakly activates pDCs to produce IFN-α. Here, we demonstrate that differences in the kinetics of TLR9 activation in human pDCs are essential for the understanding of the functional difference between CpG-A and CpG-B. While CpG-B quickly induces IFN-α production in pDCs, CpG-A stimulation results in delayed yet maximal IFN-α induction. Constitutive production of low levels of type I IFN in pDCs, acting in a paracrine and autocrine fashion, turned out to be the key mechanism responsible for this phenomenon. At high cell density, pDC-derived, constitutive type I IFN production primes pDCs for maximal TLR responsiveness. This accounts for the high activity of higher structured TLR agonists that trigger type I IFN production in a delayed fashion. Altogether, these data demonstrate that high type I IFN production by pDCs cannot be simply ascribed to cell-autonomous mechanisms, yet critically depends on the local immune context.

Keywords: CpG-A; CpG-B; TLR9; Type I IFN; pDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / virology
  • Humans
  • Interferon Type I / biosynthesis*
  • Interferon-alpha / metabolism
  • Kinetics
  • Ligands
  • Oligodeoxyribonucleotides / pharmacology
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / metabolism


  • Culture Media, Conditioned
  • Interferon Type I
  • Interferon-alpha
  • Ligands
  • Oligodeoxyribonucleotides
  • Toll-Like Receptors