Author(s):
Boonstra, André ; Rajsbaum, Ricardo ; Holman, Mary ; Marques, Rute ; Asselin-Paturel, Carine ; Pereira, João Pedro ; Bates, Elizabeth E. M. ; Akira, Shizuo ; Vieira, Paulo ; Liu, Yong-Jun ; Trinchieri, Giorgio ; O'Garra, Anne
Date: 2006
Persistent ID: http://hdl.handle.net/1822/67938
Origin: RepositóriUM - Universidade do Minho
Subject(s): Adaptor Proteins, Vesicular Transport; Animals; Bone Marrow Cells; CD8 Antigens; CpG Islands; Dendritic Cells; Interleukin-10; Interleukin-12; Macrophages; Mice; Myeloid Cells; Myeloid Differentiation Factor 88; Spleen; Toll-Like Receptors; Science & Technology
Description
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.
