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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2006-6-5
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pubmed:abstractText |
IL-12p70 is a key cytokine for the induction of Th1 immune responses. IL-12p70 production in myeloid cells is thought to be strictly controlled by T cell help. In this work we demonstrate that primary human monocytes can produce IL-12p70 in the absence of T cell help. We show that human monocytes express TLR4 and TLR8 but lack TLR3 and TLR7 even after preincubation with type I IFN. Simultaneous stimulation of TLR4 and TLR8 induced IL-12p70 in primary human monocytes. IL-12p70 production in peripheral blood myeloid dendritic cells required combined stimulation of TLR7/8 ligands together with TLR4 or with TLR3 ligands. In the presence of T cell-derived IL-4, but not IFN-gamma, stimulation with TLR7/8 ligands was sufficient to stimulate IL-12p70 production. In monocytes, type I IFN was required but not sufficient to costimulate IL-12p70 induction by TLR8 ligation. Furthermore, TLR8 ligation inhibited LPS-induced IL-10 in monocytes, and LPS alone gained the ability to stimulate IL-12p70 in monocytes when the IL-10 receptor was blocked. Together, these results demonstrate that monocytes are licensed to synthesize IL-12p70 through type I IFN provided via the Toll/IL-1R domain-containing adaptor inducing IFN-beta pathway and the inhibition of IL-10, both provided by combined stimulation with TLR4 and TLR8 ligands, triggering a potent Th1 response before T cell help is established.
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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/Antigens, CD14,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/R 848,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 7,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 8,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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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 |
15
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pubmed:volume |
176
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7438-46
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16751389-Adult,
pubmed-meshheading:16751389-Animals,
pubmed-meshheading:16751389-Antigens, CD14,
pubmed-meshheading:16751389-Cell Line,
pubmed-meshheading:16751389-Cells, Cultured,
pubmed-meshheading:16751389-Cricetinae,
pubmed-meshheading:16751389-Drug Synergism,
pubmed-meshheading:16751389-Humans,
pubmed-meshheading:16751389-Imidazoles,
pubmed-meshheading:16751389-Interleukin-10,
pubmed-meshheading:16751389-Interleukin-12,
pubmed-meshheading:16751389-Ligands,
pubmed-meshheading:16751389-Lipopolysaccharides,
pubmed-meshheading:16751389-Middle Aged,
pubmed-meshheading:16751389-Monocytes,
pubmed-meshheading:16751389-Protein Subunits,
pubmed-meshheading:16751389-Receptors, IgG,
pubmed-meshheading:16751389-Th1 Cells,
pubmed-meshheading:16751389-Toll-Like Receptor 2,
pubmed-meshheading:16751389-Toll-Like Receptor 4,
pubmed-meshheading:16751389-Toll-Like Receptor 7,
pubmed-meshheading:16751389-Toll-Like Receptor 8,
pubmed-meshheading:16751389-Toll-Like Receptors
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pubmed:year |
2006
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pubmed:articleTitle |
T cell-independent, TLR-induced IL-12p70 production in primary human monocytes.
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pubmed:affiliation |
Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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