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Kurz 2016 Abstract IOC109

From Bioblast
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 rather the antiviral immune response 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 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. 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. In addition, upon infection the isolated mitochondria show an alteration in their calcium buffering capacity and sensitivity against calcium. Furthermore, viral infection also interferes with the oxidative phosphorylation in primary hepatocytes. However, the detailed molecular mechanism and role of mitochondria in sensitizing hepatocytes is still under investigation.


Labels: Pathology: Infectious 







Reference

  1. Wohlleber D, Kashkar H, Gaertner K, Frings MK, Odenthal M, Hegenbarth S, Boerner C, Arnold B, Haemmerling G, Nieswandt B, van Rooijen N, Limmer A, Cederbrant K, Heikenwaelder M, Pasparakis M, Protzer U, Dienes HP, Kurts C, Kroenke M, Knolle PA (2012) TNF‐induced target cell killing by CTL activated through cross‐presentation. Cell Rep 2:478–87.