The effect of interferons and viral proteins on antigen-presenting cells in chronic hepatitis B

Abstract

The innate immune system forms the so-called first line of defense against invading pathogens like viruses. Innate immune cells include phagocytes like monocytes, macrophages and dendritic cells (DC). Phagocytes sample their environments, binding and taking up viral pathogens. By means of surface and intracellular recognition receptors these cells are able to recognize and react to viral pathogens by producing molecules like cytokines that attract and activate other immune cells. Furthermore, they can present pathogen-derived antigens to T cells. Therefore, they are also called antigen-presenting cells (APC). APC can induce T effector cell, but also B cell, activation and differentiation at the site of inflammation, ultimately leading to the induction of virus-specific T and B cell responses. Also in HBV infection, APC are key players in the initiation and regulation of antiviral immune responses, ensuing in combined cellular and humoral immunity that ultimately allows control of HBV infection. This thesis focuses on specific aspects of the role of APC in chronic HBV infection. Interferons, a family of cytokines, are used as antiviral therapy in chronic HBV infection, but what the exact effects of IFN on APC are and how this influences the role of APC in HBV infection remains elusive. Furthermore, APC are constantly exposed to viral proteins, but reports on their interaction with APC are scarce while literature on their effects on APC seem contradictive and/or insufficient. Therefore, we investigated effects of IFN and viral proteins on APC in chronic HBV infection to further define the role of APC in HBV infection.