| Central role of extracellular signal-regulated kinase and Toll-like receptor 4 in IL-10 production in regulatory dendritic cells induced by Trypanosoma cruzi. | |
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MedLine Citation:
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PMID: 20537708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several Trypanosoma cruzi molecules that stimulate macrophages activity were described as Toll-like receptor 2 (TLR2) ligands. Besides, the models of dendritic cells (DC) are poorly characterised. We have previously demonstrated that live-trypomastigotes (Tp) plus lipopolysaccharide (LPS) induce DC with tolerogenic properties that produce high levels of interleukin (IL)-10 and an impaired capacity to induce lymphoproliferation. Here, we show that the regulatory phenotype was observed with heat-killed trypomastigotes (Tphk) stimulation, ruling out DC infection. T. cruzi induced a particular DC activation state increasing LPS-activation of extracellular regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. Inhibition of ERK down-regulated IL-10 production and restored DC stimulatory capacity, showing the importance of this pathway in the DC modulation. A recent work shows that signalling via TLR4 and TLR2 induces a synergism in anti-inflammatory cytokine production in murine DC. Upon TLR2 and TLR4 stimulation using Pam(3)Cys or LPS and Tphk in DC from TLR2 knock out (KO) or TLR4-mutant mice, we showed that high levels of IL-10 were independent of TLR2 but associated with TLR4 and NF-kappaB signallization. Although sialic acid has been described as a molecule responsible of DC inhibition, we determine that it is not associated with T. cruzi-IL-10 modulatory response. In conclusion, all these findings demonstrate a key role of ERK and TLR4 in association with NF-kappaB in IL-10 modulation induced by T. cruzi and suggest that this regulatory effect involves parasite-DC interactions not described yet. |
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Authors:
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Carolina V Poncini; Guadalupe Giménez; Carolina A Pontillo; Catalina D Alba-Soto; Elvira L D de Isola; Isabel Piazzón; Stella M González Cappa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-26 |
Journal Detail:
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Title: Molecular immunology Volume: 47 ISSN: 1872-9142 ISO Abbreviation: Mol. Immunol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-23 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905289 Medline TA: Mol Immunol Country: England |
Other Details:
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Languages: eng Pagination: 1981-8 Citation Subset: IM |
Copyright Information:
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(c) 2010. Published by Elsevier Ltd. |
Affiliation:
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Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 13, (1121) Ciudad Autónoma de Buenos Aires, Argentina. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Dendritic Cells / immunology* Extracellular Signal-Regulated MAP Kinases / physiology* Interleukin-10 / biosynthesis* Lipopolysaccharides / pharmacology Mice Mice, Inbred Strains N-Acetylneuraminic Acid / physiology NF-kappa B / physiology Phosphorylation STAT3 Transcription Factor / metabolism Toll-Like Receptor 2 / physiology Toll-Like Receptor 4 / physiology* Trypanosoma cruzi / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/NF-kappa B; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; 0/Tlr2 protein, mouse; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 130068-27-8/Interleukin-10; 131-48-6/N-Acetylneuraminic Acid; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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