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 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.
Boonstra
André
A
Division of Immunoregulation, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
Rajsbaum
Ricardo
R
Holman
Mary
M
Marques
Rute
R
Asselin-Paturel
Carine
C
Pereira
João Pedro
JP
Bates
Elizabeth E M
EE
Akira
Shizuo
S
Vieira
Paulo
P
Liu
Yong-Jun
YJ
Trinchieri
Giorgio
G
O'Garra
Anne
A
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
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