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Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Jun 01; Vol. 172 (11), pp. 6820-7. - Publication Year :
- 2004
-
Abstract
- Unmethylated CpG DNA binds to the Toll-like receptor 9 (TLR9) and activates NF-kappaB to induce cytokine genes in dendritic cells (DCs). IFN regulatory factor (IRF)-8/IFN consensus sequence binding protein is a transcription factor important for development and activation of DCs. We found that DCs from IRF-8(-/-) mice were unresponsive to CpG and failed to induce TNF-alpha and IL-6, targets of NF-kappaB. Revealing a signaling defect selective for CpG, these cytokines were robustly induced in IRF-8(-/-) DCs in response to LPS that signals through TLR4. IRF-8(-/-) DCs expressed TLR9, adaptor myeloid differentiation factor 88, and other signaling molecules, but CpG failed to activate NF-kappaB in -/- cells. This was due to the selective inability of -/- DCs to activate I-kappaB kinase alphabeta, the kinases required for NF-kappaB in response to CpG. IRF-8 reintroduction fully restored CpG activation of NF-kappaB and cytokine induction in -/- DCs. Together, TLR signals that activate NF-kappaB are diverse among different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs.
- Subjects :
- Gene Transfer, Horizontal
Humans
I-kappa B Kinase
Interferon Regulatory Factors
Interleukin-6 biosynthesis
Mitogen-Activated Protein Kinases metabolism
Oligodeoxyribonucleotides pharmacology
Phosphorylation
Protein Serine-Threonine Kinases metabolism
Repressor Proteins genetics
Signal Transduction
Toll-Like Receptor 4
Toll-Like Receptor 9
Toll-Like Receptors
Tumor Necrosis Factor-alpha biosynthesis
p38 Mitogen-Activated Protein Kinases
Dendritic Cells physiology
Membrane Glycoproteins physiology
NF-kappa B metabolism
Receptors, Cell Surface physiology
Repressor Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15153500
- Full Text :
- https://doi.org/10.4049/jimmunol.172.11.6820