Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles
Membrane microparticles (MMP) released from apoptotic cells deliver signals that secure the anti-inflammatory response beyond the nearest proximity of the apoptotic cell. Plasmacytoid dendritic cells (pDC) are sentinels prepared to detect cellular processes that endanger the organism. They play a ke...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
11 July 2012
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| In: |
The journal of immunology
Year: 2012, Jahrgang: 189, Heft: 4, Pages: 1747-1756 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1100631 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.4049/jimmunol.1100631 Verlag, Volltext: http://www.jimmunol.org/content/189/4/1747 
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| Verfasserangaben: | Martin Schiller, Marijo Parcina, Petra Heyder, Sandra Foermer, Jenny Ostrop, Albrecht Leo, Klaus Heeg, Martin Herrmann, Hanns-Martin Lorenz, Isabelle Bekeredjian-Ding |
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| 520 | |a Membrane microparticles (MMP) released from apoptotic cells deliver signals that secure the anti-inflammatory response beyond the nearest proximity of the apoptotic cell. Plasmacytoid dendritic cells (pDC) are sentinels prepared to detect cellular processes that endanger the organism. They play a key role in the regulation of both pro- and anti-inflammatory immune responses. Based on the assumption that pDC could participate in the initiation of the anti-inflammatory response to apoptotic cells, we investigated the effects of apoptotic cell-derived MMP on human pDC. The results obtained in our experiments confirmed that MMP released from apoptotic cells trigger IFN-α secretion from human pDC. They further suggest that pDC activation results from sensing of DNA contained in MMP. MMP-DNA displays a particularly strong stimulatory activity compared with MMP-RNA and other sources of DNA. Inhibition of MMP-induced IFN-α secretion by cytochalasin D, chloroquine, and an inhibitory G-rich oligodeoxynucleotide identify TLR9 as the receptor for MMP-DNA. In marked contrast to the pDC response in autoimmune patients, in healthy subjects MMP-mediated stimulation of pDC-derived IFN-α was found to be independent of FcγRIIA (CD32A). Based on our findings, we conclude that induction of pDC-derived IFN-α by MMP is a physiological event; future investigations are necessary to elucidate whether pDC activation promotes inflammation or propagates tolerance in the context of apoptotic cell clearance. | ||
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