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  Conventional Bone Marrow-Derived Dendritic Cells Contribute to Toll-Like Receptor-Independent production of Alpha/Beta Interferon in Response to Inactivate Parapoxvirus Ovis

Siegemund, S., Hartl, A., von Buttlar, H., Dautel, F., Raue, R., Freudenberg, M. A., et al. (2010). Conventional Bone Marrow-Derived Dendritic Cells Contribute to Toll-Like Receptor-Independent production of Alpha/Beta Interferon in Response to Inactivate Parapoxvirus Ovis. Journal of Virology, 83, 9411-9422.

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Siegemund, Sabine, Autor
Hartl, Andrea, Autor
von Buttlar, Heiner, Autor
Dautel, Franziska, Autor
Raue, Rüdiger, Autor
Freudenberg, Marina A.1, Autor           
Fejer, György1, Autor           
Büttner, Mathias, Autor
Köhler, Gabriele, Autor
Kirschning, Carstens J., Autor
Sparwasser, Tim, Autor
Alber, Gottfried, Autor
Affiliations:
1Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              

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 Zusammenfassung: Parapoxvirus ovis (PPVO) is a member of the Poxviridae family and belongs to the genus Parapoxvirus. It displays only limited homology with orthopoxviruses and has some molecular features such as an unusual high GC content distinct from orthopoxviruses. Inactivated PPVO (iPPVO) displays strong immunostimulatory capacities mediating antiviral activity in vivo. The role of dendritic cells (DC) and the pattern recognition receptors and signaling requirements responsible for immunostimulation by iPPVO are unknown. We demonstrate here that bone marrow-derived plasmacytoid DC (BM-pDC) and bone marrow-derived conventional DC (BM-cDC) secrete alpha/beta interferon (IFN-α/β) in response to iPPVO. Furthermore, iPPVO induces tumor necrosis factor alpha (TNF-α) and interleukin-12/23p40 (IL-12/23p40) release and major histocompatibility complex class II (MHC-II), MHC-I, and CD86 upregulation by bone marrow-derived DC (BMDC). After engulfment, iPPVO is located in endosomal compartments and in the cytosol of BMDC. iPPVO elicits IFN-α/β by Toll-like receptor (TLR)-independent pathways in BM-cDC, since IFN-α/β release does not require myeloid differentiation primary response gene 88 (MyD88) or TIR-domain containing adaptor protein inducing interferon (TRIF). In contrast, iPPVO-induced TNF-α release and enhanced expression of MHC-I and CD86 but not of MHC-II by BMDC chiefly requires MyD88 but not TLR2 or TLR4. Induction of IFN-α by iPPVO in BM-cDC occurred in the absence of IFN regulatory factor 3 (IRF3) but required the presence of IRF7, whereas iPPVO-triggered IFN-β production required the presence of either IRF7 or IRF3. These results provide the first evidence that iPPVO mediates its immunostimulatory properties by TLR-independent and TLR-dependent pathways and demonstrate an important role of cDC for IFN-α/β production.

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Sprache(n): eng - English
 Datum: 2010
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 464628
 Art des Abschluß: -

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Titel: Journal of Virology
  Alternativer Titel : J. Virol.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 83 Artikelnummer: - Start- / Endseite: 9411 - 9422 Identifikator: -