Differential requirement for the IKKß/NF-κB signaling module in regulating TLR- versus RLR-induced type 1 IFN expression in dendritic cells.
J Immunol
; 193(5): 2538-45, 2014 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25057006
ABSTRACT
Host innate-immune responses are tailored by cell type to control and eradicate specific infectious agents. For example, an acute RNA virus infection can result in high-level expression of type 1 IFNs by both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs), but whereas cDCs preferentially use RIG-I-like receptor (RLR) signaling to produce type 1 IFNs, pDCs predominantly use TLRs to induce these cytokines. We previously found that the IκB kinase ß (IKKß)/NF-κB pathway regulates early IFN-ß expression, but not the magnitude of type 1 IFN expression following RLR engagement. In this study, we use IKKß inhibition and mice deficient in IKKß or canonical NF-κB subunits (p50, RelA/p65, and cRel) to demonstrate that the IKKß/NF-κB axis is critical for virus-induced type 1 IFN expression in pDCs, but not in cDCs. We also reveal a crucial and more general requirement for IKKß/NF-κB in TLR- but not RLR-induced expression of type 1 IFNs and inflammatory cytokines. Together, these findings reveal a previously unappreciated specificity of the IKKß/NF-κB signaling axis in regulation of antimicrobial responses by different classes of pattern recognition receptors, and therefore by individual cell types reliant on particular pattern recognition receptors for their innate-immune transcriptional responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
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Células Dendríticas
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Transdução de Sinais
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Interferon Tipo I
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Regulação da Expressão Gênica
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NF-kappa B
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Quinase I-kappa B
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Receptores Toll-Like
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article