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Science. 2010 Sep 17;329(5998):1530-4. doi: 10.1126/science.1187029.

Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3.

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1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

Endosomal Toll-like receptors (TLRs) 7 and 9 recognize viral pathogens and induce signals leading to the activation of nuclear factor κB (NF-κB)-dependent proinflammatory cytokines and interferon regulatory factor 7 (IRF7)-dependent type I interferons (IFNs). Recognition of viral nucleic acids by TLR9 requires its cleavage in the endolysosomal compartment. Here, we show that TLR9 signals leading to the activation of type I IFN, but not proinflammatory cytokine genes, require TLR9 trafficking from endosomes to a specialized lysosome-related organelle. Furthermore, we identify adapter protein-3 as the protein complex responsible for the trafficking of TLR9 to this subcellular compartment. Our results reveal an intracellular mechanism for bifurcation of TLR9 signals by selective receptor trafficking within the endosomal system.

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PMID:
20847273
PMCID:
PMC3063333
DOI:
10.1126/science.1187029
[Indexed for MEDLINE]
Free PMC Article

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