Compartment-specific control of signaling from a DNA-sensing immune receptor

Sci Signal. 2010 Nov 30;3(150):pe45. doi: 10.1126/scisignal.3150pe45.


Many cell signaling events are spatially organized, enabling control of specificity, amplitude, and duration. Toll-like receptor 9 (TLR9) binds to nucleic acid sequences present in bacteria or DNA viruses and initiates a signaling pathway that culminates in the transcriptional induction of genes important for host defense, such as those encoding proinflammatory cytokines and type I interferon. A specialized membrane trafficking pathway has been described that is required for a specific branch of TLR9 signaling: the production of type I interferon. Cells deficient for the clathrin adaptor complex AP-3 failed to traffic TLR9 to a specific endosomal compartment and were unable to produce type I interferon despite normal increases in the abundance of interleukin-12p40, a proinflammatory cytokine. These findings support a model in which the targets of TLR9 engagement are controlled by the compartment in which TLR9 is activated.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA, Bacterial / immunology*
  • DNA, Bacterial / metabolism
  • DNA, Viral / immunology*
  • DNA, Viral / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / immunology
  • Humans
  • Interferon Type I / biosynthesis
  • Interferon Type I / immunology
  • Interleukin-12 Subunit p40 / biosynthesis
  • Interleukin-12 Subunit p40 / immunology
  • Signal Transduction / immunology*
  • Toll-Like Receptor 9 / immunology*
  • Toll-Like Receptor 9 / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / immunology
  • Transcription, Genetic / immunology


  • DNA, Bacterial
  • DNA, Viral
  • DNA-Binding Proteins
  • IL12B protein, human
  • Interferon Type I
  • Interleukin-12 Subunit p40
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Transcription Factors
  • enhancer-binding protein AP-3