Kurz 2016 Abstract IOC109: Difference between revisions
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| Kurz S, Wohlleber D, Knolle PA (2016) Mitochondria as immune sensors of viral infection in hepatocytes. Mitochondr Physiol Network 21.01. |
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Kurz S, Wohlleber D, Knolle PA (2016)
Event: IOC109
Hepatotropic viruses, such as Hepatitis B virus (HBV) and Hepatitis C virus (HCV), are a global health problem and can induce severe liver disease. However, HBV and HCV are non-cytopathic viruses, it is rather the antiviral immune response that induces the liver inflammation and disease. Recognition and elimination of virus-infected hepatocytes occurs by antigen presentation of viral antigens on MHC class I molecules to virus-specific CD8 T effector cells (CTLs). Therefore, some viruses have gained strategies to evade the immune response through interfering with MHC class I mediated antigen presentation. Wohlleber et al. (2012) demonstrated a novel cytotoxic CTL effector mechanisms, the non-canonical CTL effector function [1]. Thereby cross-presentation of viral antigens by non-infected liver sinusoidal endothelial cells (LSEC) stimulates CTLs to secrete TNF. CTL-derived TNF selectively induces apoptosis in infected hepatocytes but not in non-infected hepatocytes. As non-infected LSEC cross-present hepatocyte derived viral antigens, this circumvents viral immune evasion in infected hepatocytes.
Based on the specificity of TNF-induced apoptosis for virus-infected hepatocytes, viral infection sensitizes hepatocytes towards TNF-induced apoptosis. Several observations indicate a central role of mitochondria in this pro-apoptotic signaling. Mitochondria are the central organelles for energy metabolism and Ca2+ homeostasis but also in the apoptotic signaling cascade in hepatocytes with which the viral infection interferes. First, viral infection enhances the cytochrome c release from mitochondria upon TNF stimulation and thereby facilitating apoptosis induction. Furthermore, viral infection also changes the oxidative respiration of isolated mitochondria as well as primary hepatocytes. In addition, upon infection the isolated mitochondria show a decreased calcium buffering capacity followed by increased sensitivity against calcium. However, the detailed molecular mechanism and role of mitochondria in sensitizing hepatocytes is still under investigation.
Labels: Pathology: Infectious
