title: 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.
abstract: 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.
authors.affiliation: Division of Immunoregulation, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rajsbaum
authors.forename: Mary
authors.initials: M
authors.lastname: Holman
authors.forename: Rute
authors.initials: R
authors.lastname: Marques
authors.forename: Carine
authors.initials: C
authors.lastname: Asselin-Paturel
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Pereira
authors.forename: Elizabeth E M
authors.initials: EE
authors.lastname: Bates
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Paulo
authors.initials: P
authors.lastname: Vieira
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Anne
authors.initials: A
authors.lastname: O'Garra
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016827:CD8 Antigens; D016753:Interleukin-10; D018664:Interleukin-12; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C409469:CD8 antigen, alpha chain; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse