Between Scylla and Charybdis: The role of the human immune system in the pathogenesis of hepatitis C

Figure 1 Central role of natural killer cells in the pathogenesis of hepatitis C. Natural killer (NK) cells regulate fibrosis by killing of activated hepatic stellate cells (HSC), which trigger NK cell activation via natural killer cell receptor with extracellular C-type lectin domains (NKG2D) signalling. The release of granzyme/perforin and cytotoxic cytokines, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce tissue damage. Interferon-γ (IFN-γ) released from NK cells can clear hepatitis C virus (HCV) infection from infected hepatocytes without cytolysis. On the other hand NK cell activity is critically dependent on sufficient supply with interleukin 2 (IL-2) from CD4⁺ T cells.