title: Identification of Toll-like receptor 9 as parapoxvirus ovis-sensing receptor in plasmacytoid dendritic cells.
abstract: Parapoxvirus ovis (PPVO) is known for its immunostimulatory capacities and has been successfully used to generate vector vaccines effective especially in non-permissive host species. Murine conventional and plasmacytoid dendritic cells (cDC and pDC) are able to recognize PPVO. The PPVO-sensing receptor on pDC is hitherto unknown. In this study we aimed to define the pattern recognition receptor responsible for the activation of murine pDC by inactivated and replication-competent PPVO. We show that PPVO-induced expression of type I and type III interferons, pro-inflammatory cytokines, and co-stimulatory CD86 by bone marrow-derived pDC but not cDC is blocked by chloroquine, an inhibitor of endosomal maturation. The activation of pDC is independent of viral replication and depends mainly on TLR9. Moreover, the use of phosphatidylinositol 3-kinase inhibitor wortmannin or C-Jun-N-terminal kinase inhibitor SP600125 results in significant reduction of PPVO-induced pDC activation. Taken together, our data identify endosomal TLR9 as PPVO-sensing receptor in pDC.
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: von Buttlar
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Siegemund
authors.affiliation: Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Büttner
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Alber
mesh_terms: D000563:Amebicides / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D011992:Endosomes / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018157:Parapoxvirus / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D011213:Poxviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
chemical_list: D000563:Amebicides; D000873:Anthracenes; D016207:Cytokines; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C432165:pyrazolanthrone; D002738:Chloroquine; D048031:JNK Mitogen-Activated Protein Kinases