Regulation of acute hepatitis
About this project
The pathogenesis of virus-induced hepatitis is not well understood and immunological strategies aiming at re-adjustment of immunological processes within the liver are not available, yet. Recently we studied why upon enterovirus infection very divergent disease courses can be detected, ranging from mild symptoms to severe myocarditis. We found that upon Coxsackievirus B3 (CVB3) infection of mice hepatocytes are key innate effector cells that mount protective type I IFN responses. In conditional mice devoid of type I IFN receptor signaling selectively on hepatocytes, CVB3 infection is not controlled and the virus disseminates similarly as in mice devoid of the type I IFN receptor in all cells (Koestner et al., 2018). Furthermore, we analyzed how liver resident Kupffer cells and infiltrating peripheral myeloid cells react upon hepatic infection (Borst et al., 2018). To this end, we studied vaccina virus as well as MCMV infection of mice. Interestingly, right after infection Kupffer cells disappear from the liver, whereas peripheral myeloid cells infiltrate the liver and later differentiated to cells that are very reminiscent to Kupffer cells. Furthermore, type I IFN receptor signaling of myeloid cells modulates the severity of hepatitis, whereas type I IFN receptor signaling of hepatocytes has no effect, at least in VACV and MCMV induced hepatitis. Currently it is analyzed how infiltrated myeloid cells differentiate to cells that are reminiscent of Kupffer cells within the liver. The long term objective of these studies is to better understand local immune mechanisms within the liver that modulate anti-viral defense and inflammation. It is planned to use these models in order to study new tracers for in vivo imaging. Such data will help to develop new diagnostic tools in the clinics.
