The interaction of Hepatitis B virus infection and Schistosomiasis in chronic pathogen-induced liver inflammation

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One of the main complications of hepatitis B virus (HBV) infection is the development of chronic hepatitis after an acute infection, and patients with chronic hepatitis B are at high risk to develop liver cirrhosis and hepatocellular carcinoma (HCC). Interestingly, chronic hepatitis B and also HCC develop at a higher frequency in developing countries in which co-infections with several helminth (worm) species such as the human pathogen Schistosoma mansoni (the causative agent for bilharzia) are common. Helminths cause chronic infections and to establish these they have developed strong immuneregulatory and even suppressive capacities. During co-infection these may contribute to HBV persistence by compromising anti-viral immune responses, and to liver disease progression. Schistosome-induced immune responses, however, are very dynamic and range from an acute, inflammatory to a chronic, anti-inflammatory (Th2) and immuneregulatory phase where suppressor cells like regulatory T cells (Treg) play an important role. We believe that this circumstance, as well as the fact that S. mansoni also causes liver disease, could lead to very different outcomes of concomitant acute and chronic HBV infection. Therefore, the main objectives within this proposal are to investigate in detail the impact of the acute and chronic immune phases induced during preexisting S. mansoni infection on the outcome of acute HBV infection and in correlation, the impact of subsequent S. mansoni infection on preexisting, chronic HBV infection with a special focus on the cellular processes within the liver since this organ is mainly affected by both pathogens. The results will deepen our understanding why HBV chronicity rates are much higher in third world (helminth-endemic) countries compared to industrialized ones. In the future, this may have direct impact on world-wide treatment and vaccination efforts for hepatitis B, which currently disregard the role of helminth co-infections.