HEPATOTROPIC INFECTIOUS AGENTS AND ENVIRONMENTAL COFACTORS

Diseases related to infections by pathogenic hepatotropic viruses such as HBV and HCV or by parasites such as Leishmania constitute real public health problems. The aim of our team is to understand how hepatotropic infectious agents induce hepatitis and liver damages by studying how Hepatitis B and C viruses enter hepatocytes and how the infected cells respond. Furthermore, we investigate the role of cellular and molecular actors of the innate immunity in the pathophysiology of hepatitis and of Leishmania infection. Our research project aims to identify  molecular targets for new anti-infective or therapeutic strategies.

To this end, we develop two main axes of research:

Host-pathogen interactions of Hepatitis B and C viruses. Our goal is to determine the role of different domains within the HBV envelope proteins during the different stages of HBV entry into hepatocytes (fusion and translocation). Morevover, we aim at identifying cellular proteins required for HCV entry into the host cell.

Role of cytokines and immune cells in hepatitis. Our team studies more particularly the role i) of cytokines, such as prokineticines, IL-33, IL-31 and their  receptors, as well as immunomodulatory factors such as HLA-G; ii) of immune cells such as dendritic cells and NKT lymphocytes, in human and murine hepatitis. In order to understand their in vivo roles  we developed mouse models of acute and chronic hepatitis induced by toxic agents or by infection with hepatotrop parasites such as Leishmania. We have selected cytokine- and iNKT cell-deficient mouse models to analyze their role in the immune response associated with toxic agents-induced hepatitis or in the granulomatous reaction associated with Leishmania donovani infection.