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Volume 23 Issue 2
April 2008
    Citation: Jun Wu, Ruth Bröring, Jörg F. Schlaak. The Role of the Innate Immune System of the Liver in the Control of HBV and HCV* .VIROLOGICA SINICA, 2008, 23(2) : 116-123.  http://dx.doi.org/10.1007/s12250-008-2942-y
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    The Role of the Innate Immune System of the Liver in the Control of HBV and HCV*

    • Department of Gastroenterology, University Hospital of Essen, 45122 Essen, Germany

    • Corresponding author: Jörg F. Schlaak, joerg.schlaak@uni-due.de
    • Received Date: 25 November 2007
      Accepted Date: 24 January 2008
      Available online: 01 April 2008

      Fund Project: The Deutsche Forschungsgemeinschaft SCHL 377/2-2

    • Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are among the most frequent causes of chronic liver disease worldwide. As recent studies suggested that Toll like receptor (TLR)-based therapies may represent a promising approach in the treatment of HBV infection, we have studied the role of the local innate immune system of the liver as possible mediator of this effect. Murine non-parenchymal liver cells (NPC; Kupffer cells, KC; sinusoidal endothelial cells, LSEC) were isolated from C57/BL6 and stimulated by TLR 1-9 agonists. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells and HCV in the murine HCV replicon cell line MH1. Only supernatants from TLR 3 and -4 stimulated KC and TLR 3 stimulated LSEC were able to potently suppress HBV and HCV replication. By using neutralizing antibodies we could demonstrate that the TLR 3- but not the TLR 4 mediated effect is exclusively mediated through IFN-β. Our data indicate that TLR 3 and -4 mediated stimulation of NPC leads to production of IFN-β which can potently suppress HBV and HCV replication. This is of relevance for the local control of viral hepatitis infection by the innate immune system of the liver, the development of novel TLR-based therapeutic approaches and sheds new light on the viral crosstalk between HCV (TLR 3 stimulator) and HBV.
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      The Role of the Innate Immune System of the Liver in the Control of HBV and HCV*

        Corresponding author: Jörg F. Schlaak, joerg.schlaak@uni-due.de
      • Department of Gastroenterology, University Hospital of Essen, 45122 Essen, Germany
      • Received Date: 25 November 2007
      • Accepted Date: 24 January 2008
      Fund Project:  The Deutsche Forschungsgemeinschaft SCHL 377/2-2

      Abstract: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are among the most frequent causes of chronic liver disease worldwide. As recent studies suggested that Toll like receptor (TLR)-based therapies may represent a promising approach in the treatment of HBV infection, we have studied the role of the local innate immune system of the liver as possible mediator of this effect. Murine non-parenchymal liver cells (NPC; Kupffer cells, KC; sinusoidal endothelial cells, LSEC) were isolated from C57/BL6 and stimulated by TLR 1-9 agonists. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells and HCV in the murine HCV replicon cell line MH1. Only supernatants from TLR 3 and -4 stimulated KC and TLR 3 stimulated LSEC were able to potently suppress HBV and HCV replication. By using neutralizing antibodies we could demonstrate that the TLR 3- but not the TLR 4 mediated effect is exclusively mediated through IFN-β. Our data indicate that TLR 3 and -4 mediated stimulation of NPC leads to production of IFN-β which can potently suppress HBV and HCV replication. This is of relevance for the local control of viral hepatitis infection by the innate immune system of the liver, the development of novel TLR-based therapeutic approaches and sheds new light on the viral crosstalk between HCV (TLR 3 stimulator) and HBV.

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      IMMUNE SYSTEM OF THE LIVER – NON-PARENCHYMAL LIVER CELLS