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Download Tick-borne encephalitis virus (TBEV) is the most prevalent arbovirus
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Transcript
Interaction of tick-borne encephalitis virus with human myeloid- and plasmacytoid dendritic cells Bastian Dörrbecker1, Thorsten Volgmann2, Gerhardt Dobler3, Martin Pfeffer4, Martin Spiegel1 and Frank T. Hufert1 1 Georg-August-University of Göttingen; University Medical Center Göttingen, Institut für Virologie, Kreuzbergring 57, Göttingen, 37075, Germany 2 DRK-Blutspendedienst NSTOB gemeinnützige GmbH der Landesverbände Niedersachsen, Sachsen-Anhalt, Oldenburg, Bremen und Thüringen; Eldagsener Strasse 38; 31830 Springe 3 Bundeswehr Institute of Microbiology, Department of Virology and Rickettsiology, Neuherbergstrasse 1, D-80937 Munich, Germany 4 University of Leipzig; Institute of Animal and Veterinary Public Health; in the Centre of Veterinary Public Health; An den Tierkliniken 1; 04103 Leipzig Keywords: Dendritic Cells, tick-borne encephalitis virus, inflammatory cytokines, interferonα Tick-borne encephalitis virus (TBEV) is the most prevalent arbovirus in Europe and in many parts of Asia. Clinical symptoms range from mild fever to severe neurological disorders. However, the pathogenesis of TBEV is still not completely understood, mechanisms of virus host response interaction and principles of neuroinvasion remain to be elucidated. Dentritic cells (DCs) are the most potent antigen-presenting cells and very important components for the immune system in terms of infections with pathogens including viruses. Corresponding to their function DC are divided into two main subtypes, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). Whereas activated pDCs play an important role as main type I interferon (type I IFN)-producing cells and represent a link of innate and adaptive immune response, mDCs are the main antigen-presenting DC subtype playing a decisive role in the adaptive immune response. We analyzed the interaction of human mDCs and pDCs with the highly virulent TBEV strain Hypr. TBEV infected pDCs produced high amounts of interferon- (IFN-) α as well as inflammatory cytokines interleukin-6 (IL-6), IL-8 and tumour necrosis factor-α (TNF-α). At the same time pDCs exhibited only a transient upregulation of surface molecule markers (adhesion markers CD54, CD58, maturation marker CD83, co-stimulatory and activation markers CD40, CD80, CD86, apoptosis marker CD95 as well as antigen-presenting complexes MHCI and MHCII) but were capable to restrict TBEV replication. This restriction could be overcome by preincubation of pDCs with an antibody blocking the interferon / receptor indicating that the high levels of IFN produced by pDCs protect themselves from TBEV infection. In contrast, IFN-α production by mDC is 10-fold lower in response to TBEV while they also produce high amounts of IL-6, IL-8, TNF-α and additionally IL-1β. In contrast to pDCs, mDCs showed impaired activation of surface molecule expression and supported productive TBEV replication. It is therefore tempting to speculate, that productively TBEV-infected mDCs disseminate the virus in the infected host but fail to prime and activate TBEV-specific T-cells properly.