Compartment-specific control of signaling from a DNA-sensing immune receptor.
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.
Division of Immunology and Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720, USA.
Alex
A
Engel
Gregory M
GM
Barton
D000818:Animals; D004269:DNA, Bacterial / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D004269:DNA, Bacterial; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C500879:IL12B protein, human; D007370:Interferon Type I; D053762:Interleukin-12 Subunit p40; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014157:Transcription Factors; C060759:enhancer-binding protein AP-3