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

André Boonstra, Ricardo Rajsbaum Gorodezky, Mary Holman, Rute Marques, Carine Asselin-Paturel, João Pedro Pereira, Elizabeth E M Bates, Shizuo Akira, Paulo Vieira, Yong Jun Liu, Giorgio Trinchieri, Anne O'Garra

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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 CD8α- and CD8α+ DC. Although plasmacytoid DC did not produce EL-10 upon stimulation, addition of this cytokine exogenously suppressed their production of IL-12, TNF, and IFN-α, showing trans but not autocrine regulation of these cytokines by IL-10 in plasmacytoid DC.

Original languageEnglish (US)
Pages (from-to)7551-7558
Number of pages8
JournalJournal of Immunology
Volume177
Issue number11
StatePublished - Dec 1 2006
Externally publishedYes

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Myeloid Cells
Interleukin-10
Dendritic Cells
Macrophages
Cytokines
Ligation
Interleukin-1 Receptors
Interleukin-12
Bone Marrow
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Boonstra, André; Rajsbaum Gorodezky, 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.

In: Journal of Immunology, Vol. 177, No. 11, 01.12.2006, p. 7551-7558.

Research output: Contribution to journalArticle

Boonstra, A, Rajsbaum Gorodezky, R, Holman, M, Marques, R, Asselin-Paturel, C, Pereira, JP, Bates, EEM, Akira, S, Vieira, P, Liu, YJ, Trinchieri, G & O'Garra, A 2006, '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', Journal of Immunology, vol. 177, no. 11, pp. 7551-7558.
Boonstra, André ; Rajsbaum Gorodezky, 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. / 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. In: Journal of Immunology. 2006 ; Vol. 177, No. 11. pp. 7551-7558.
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T1 - 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

AU - Boonstra, André

AU - Rajsbaum Gorodezky, Ricardo

AU - Holman, Mary

AU - Marques, Rute

AU - Asselin-Paturel, Carine

AU - Pereira, João Pedro

AU - Bates, Elizabeth E M

AU - Akira, Shizuo

AU - Vieira, Paulo

AU - Liu, Yong Jun

AU - Trinchieri, Giorgio

AU - O'Garra, Anne

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N2 - 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 CD8α- and CD8α+ DC. Although plasmacytoid DC did not produce EL-10 upon stimulation, addition of this cytokine exogenously suppressed their production of IL-12, TNF, and IFN-α, showing trans but not autocrine regulation of these cytokines by IL-10 in plasmacytoid DC.

AB - 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 CD8α- and CD8α+ DC. Although plasmacytoid DC did not produce EL-10 upon stimulation, addition of this cytokine exogenously suppressed their production of IL-12, TNF, and IFN-α, showing trans but not autocrine regulation of these cytokines by IL-10 in plasmacytoid DC.

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