TLR4 ligands induce IFN-alpha production by mouse conventional dendritic cells and human monocytes after IFN-beta priming.
J Immunol
; 182(2): 820-8, 2009 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-19124725
ABSTRACT
Exacerbation of disease in systemic lupus erythematosus (SLE) is associated with bacterial infection. In conventional dendritic cells (cDCs), the TLR4 ligand bacterial LPS induces IFN-beta gene expression but does not induce IFN-alpha. We hypothesized that when cDCs are primed by cytokines, as may frequently be the case in SLE, LPS would then induce the production of IFN-alpha, a cytokine believed to be important in lupus pathogenesis. In this study we show that mouse cDCs and human monocytes produce abundant IFN-alpha following TLR4 engagement whether the cells have been pretreated either with IFN-beta or with a supernatant from DCs activated by RNA-containing immune complexes from lupus patients. This TLR4-induced IFN-alpha induction is mediated by both an initial TRIF-dependent pathway and a subsequent MyD88-dependent pathway, in contrast to TLR3-induced IFN-alpha production, which is entirely TRIF-dependent. There is also a distinct requirement for IFN regulatory factors (IRFs), with LPS-induced IFN-alpha induction being entirely IRF7- and partially IRF5-dependent, in contrast to LPS-induced IFN-beta gene induction which is known to be IRF3-dependent but largely IRF7-independent. This data demonstrates a novel pathway for IFN-alpha production by cDCs and provides one possible explanation for how bacterial infection might precipitate disease flares in SLE.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Monócitos
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Lipopolissacarídeos
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Interferon beta
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Interferon-alfa
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Receptor 4 Toll-Like
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article