The Host–pathogen Interaction during HBV Infection: Immunological Controversies

HBV is a hepatotropic and non-cytopathic virus that causes more than one million deaths annually from liver cirrhosis and hepatocellular carcinoma. As the virus itself is non-cytopathic, it is widely accepted that both viral control and liver pathology are mediated by the host immune system. Until recently, the focus has been on the crucial role of adaptive immune responses in controlling HBV infection, but the potential contribution of the innate system is now an important area of controversy. Unanswered questions include whether and when HBV can trigger components of innate immunity, and whether HBV can actively suppress the induction of innate immunity. We discuss the data available from animal models and human HBV infection addressing the role of innate immunity in the first part of this review. In the second part, we address the immunopathogenesis of the inflammatory events that characterize chronic hepatitis B. The mechanisms thought to be responsible for liver inflammation, namely the intrahepatic recruitment of inflammatory cells, which is orchestrated by chemokines, have been described; however, the underlying immunological triggers are much less clear. The prevailing idea is that liver inflammation results from a recovery of HBV-specific T-cells directly causing liver injury, but this scenario is supported by scanty experimental data. By contrast, recent findings raise the possibility of a contribution from innate components, such as natural killer cells.