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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2002-6-21
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pubmed:abstractText |
Type I IFN regulates different aspects of the immune response, inducing a cell-mediated immunity. We have recently shown that the infection of dendritic cells (DC) with Mycobacterium tuberculosis (Mtb) induces IFN-alpha. In this work we have monitored a rapid induction of IFN-beta followed by the delayed production of the IFN-alpha1 and/or -alpha13 subtypes. The Mtb infection rapidly activates the NF-kappaB complex and stimulates the phosphorylation of IFN regulatory factor (IRF)-3, events known to induce IFN-beta expression in viral infection. In turn, the autocrine production of IFN-beta induces the IFN-stimulated genes that contain binding sites for activated STATs in their promoters. Among the IFN-stimulated genes induced in DC through STAT activation are IRF-1 and IRF-7. The expression of IRF-1 appears to be dependent on the sequential activation of NF-kappaB and STAT-1. Once expressed, IRF-1 may further stimulate the transcription of IFN-beta. Induction of IRF-7 is also regulated at the transcriptional level through the binding of phosphorylated STAT-1 and STAT-2, forming the IFN-stimulated gene factor-3 complex. In turn, the IRF-1 and IRF-7 expression appears to be required for the delayed induction of the IFN-alpha1/13 genes. Although correlative, our results strongly support the existence of a cascade of molecular events in Mtb-infected DC. Upon infection, constitutively expressed NF-kappaB and IRF-3 are activated and likely contribute to the rapid IFN-beta expression. In turn, IFN-beta-induced IRF-1 and IRF-7 may cooperate toward induction of IFN-alpha1/13 if infection persists and these factors are activated.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
366-74
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12077266-Cells, Cultured,
pubmed-meshheading:12077266-DNA-Binding Proteins,
pubmed-meshheading:12077266-Dendritic Cells,
pubmed-meshheading:12077266-Gene Expression Regulation,
pubmed-meshheading:12077266-Humans,
pubmed-meshheading:12077266-Interferon Regulatory Factor-1,
pubmed-meshheading:12077266-Interferon Type I,
pubmed-meshheading:12077266-Interferon-alpha,
pubmed-meshheading:12077266-Interferon-beta,
pubmed-meshheading:12077266-Kinetics,
pubmed-meshheading:12077266-Mycobacterium tuberculosis,
pubmed-meshheading:12077266-NF-kappa B,
pubmed-meshheading:12077266-Phosphoproteins,
pubmed-meshheading:12077266-Phosphorylation,
pubmed-meshheading:12077266-STAT1 Transcription Factor,
pubmed-meshheading:12077266-STAT2 Transcription Factor,
pubmed-meshheading:12077266-Signal Transduction,
pubmed-meshheading:12077266-Trans-Activators
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pubmed:year |
2002
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pubmed:articleTitle |
Selective expression of type I IFN genes in human dendritic cells infected with Mycobacterium tuberculosis.
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pubmed:affiliation |
Laboratory of Immunology, Istituto Superiore di Sanità, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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