to be announced
Dept of Microbiology
Impact of chronic hepatitis on DC/T cell functions in viral infections
A common clinical complication in patients with liver cirrhosis is exacerbation to viral and bacterial infections, which often persist in these patients. Yet, the underlying cellular and molecular mechanisms have not been elucidated. Using the murine bile-duct ligation and the carbon tetrachloride model for the induction of liver fibrosis, we have demonstrated that liver cirrhosis rendered mice more susceptible to viral LCMV infection and that these mice were not able to clear the virus leading to persistent infection, recapitulating the situation in humans. This indicates that cirrhosis negatively affects systemic anti-viral host defence and the clearance of viral infections. In this project we aim to unravel the impact of chronic liver inflammation on the anti-viral immunity. Using LCMV and influenza A virus (IAV) infection models we will investigate the impact of liver cirrhosis on the phenotype and function of antigen presenting dendritic cells (DCs) and virus specific CD8+ and CD4+ T cells, which are crucial for the control of viral infections. By joining the expertise of Abdullah on chronic inflammation in the liver and LCMV infection models with that of La Gruta on IAV infection models and CTL responses we aim to elucidate the cellular and molecular mechanisms underlying the impaired anti-viral immune responses in cirrhosis. We will clarify how chronic liver inflammation may affect viral antigen presentation by DC and its impact on induction, expansion and function of CD4+ T helper cells and cytotoxic CD8+ T cells. The results of these studies will give insight into how chronic inflammation promotes viral persistence and could lay the groundwork for generating novel options for treatment of chronic viral infections.