Innate immune mechanisms responsible for controlling viral infections within the liver have largely been attributed to resident macrophages of the liver known as Kupffer cells. However, all liver cells are equipped with innate immune functions, including hepatocytes. In this study, we aimed to elucidate the role of hepatocyte-derived innate immune signaling for viral clearance using mice which lack NFκB signaling specifically in hepatocytes (IkkβΔHep mice). Infection of IkkβΔHep mice with LCMV-WE, a non-cytopathic systemic virus, led to an increased hepatic viral titers, reduced interferon signaling and diminished cytotoxic CD8+ T cell responses compared to wild-type mice. A similar phenotype was found in mice lacking interferon signaling specifically in hepatocytes (IFNARΔHep mice) infected with LCMV-WE, indicating a link between NFκB and interferon signaling in hepatocytes. These results clearly indicate that the Kupffer cells are not the only cell type that is required for efficient viral clearance in the liver and hepatocyte-intrinsic NFκB mediated interferon signaling plays a pivotal role in hepatic viral clearance, as well.      «

Innate immune mechanisms responsible for controlling viral infections within the liver have largely been attributed to resident macrophages of the liver known as Kupffer cells. However, all liver cells are equipped with innate immune functions, including hepatocytes. In this study, we aimed to elucidate the role of hepatocyte-derived innate immune signaling for viral clearance using mice which lack NFκB signaling specifically in hepatocytes (IkkβΔHep mice). Infection of IkkβΔHep mice with LCMV-W...     »