Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles

• Verfasst von: Schiller, Martin [VerfasserIn]
• Verfasst von: Parčina, Marijo [VerfasserIn]
• Verfasst von: Heyder, Petra [VerfasserIn]
• Verfasst von: Förmer, Sandra [VerfasserIn]
• Verfasst von: Ostrop, Jenny [VerfasserIn]
• Verfasst von: Leo, Albrecht [VerfasserIn]
• Verfasst von: Heeg, Klaus [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Bekeredjian-Ding, Isabelle [VerfasserIn]
• Titel: Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles
• Verf.angabe: Martin Schiller, Marijo Parcina, Petra Heyder, Sandra Foermer, Jenny Ostrop, Albrecht Leo, Klaus Heeg, Martin Herrmann, Hanns-Martin Lorenz, Isabelle Bekeredjian-Ding
• E-Jahr: 2012
• Jahr: 11 July 2012
• Umfang: 10 S.
• Fussnoten: Gesehen am 04.05.2018
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Rockville, Md. : American Association of Immunologists, 1916
• Jahr Quelle: 2012
• Band/Heft Quelle: 189(2012), 4, Seite 1747-1756
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1100631
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1572643560

Abstract

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.