Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals

We have previously reported that mouse plasmacytoid dendritic cells (DC) produce high levels of IL-12p70, whereas bone marrow-derived myeloid DC and splenic DC produce substantially lower levels of this cytokine when activated with the TLR-9 ligand CpG. We now show that in response to CpG stimulatio...

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Detalhes bibliográficos
Autor principal: Boonstra, André (author)
Outros Autores: Rajsbaum, Ricardo (author), Holman, Mary (author), Marques, Rute (author), Asselin-Paturel, Carine (author), Pereira, João Pedro (author), Bates, Elizabeth E. M. (author), Akira, Shizuo (author), Vieira, Paulo (author), Liu, Yong-Jun (author), Trinchieri, Giorgio (author), O'Garra, Anne (author)
Formato: article
Idioma:eng
Publicado em: 2006
Assuntos:
Texto completo:http://hdl.handle.net/1822/67938
País:Portugal
Oai:oai:repositorium.sdum.uminho.pt:1822/67938
Descrição
Resumo:We have previously reported that mouse plasmacytoid dendritic cells (DC) produce high levels of IL-12p70, whereas bone marrow-derived myeloid DC and splenic DC produce substantially lower levels of this cytokine when activated with the TLR-9 ligand CpG. We now show that in response to CpG stimulation, high levels of IL-10 are secreted by macrophages, intermediate levels by myeloid DC, but no detectable IL-10 is secreted by plasmacytoid DC. MyD88-dependent TLR signals (TLR4, 7, 9 ligation), Toll/IL-1 receptor domain-containing adaptor-dependent TLR signals (TLR3, 4 ligation) as well as non-TLR signals (CD40 ligation) induced macrophages and myeloid DC to produce IL-10 in addition to proinflammatory cytokines. IL-12p70 expression in response to CpG was suppressed by endogenous IL-10 in macrophages, in myeloid DC, and to an even greater extent in splenic CD8alpha(-) and CD8alpha(+) DC. Although plasmacytoid DC did not produce IL-10 upon stimulation, addition of this cytokine exogenously suppressed their production of IL-12, TNF, and IFN-alpha, showing trans but not autocrine regulation of these cytokines by IL-10 in plasmacytoid DC.