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

乙型肝炎病毒(HBV)感染的主要并发症之一是急性感染后发展为慢性肝炎，慢性乙肝患者发展为肝硬化和肝细胞癌(HCC)的风险很高。有趣的是，慢性乙肝和肝细胞癌在发展中国家发展的频率更高，在这些国家，与几种蠕虫(蠕虫)物种的混合感染是常见的，例如人类病原体曼氏血吸虫(引起比哈兹病的病原体)。蠕虫引起慢性感染，为了建立这些感染，它们发展了强大的免疫调节能力，甚至抑制能力。在合并感染期间，这些病毒可能通过损害抗病毒免疫反应而导致乙肝病毒的持续存在，并导致肝病的进展。然而，血吸虫诱导的免疫反应是非常动态的，范围从急性炎症到慢性抗炎(Th2)和免疫调节阶段，其中调节性T细胞(Treg)等抑制细胞发挥重要作用。我们认为，这种情况，以及曼氏葡萄球菌也会导致肝病的事实，可能会导致伴随着急性和慢性乙肝病毒感染的截然不同的结果。因此，这项建议的主要目的是详细调查在先前存在的曼氏血吸虫感染期间诱导的急性和慢性免疫阶段对急性乙肝病毒感染结局的影响，以及相关的后续曼氏血吸虫感染对先前存在的慢性乙肝病毒感染的影响，特别关注肝脏内的细胞过程，因为肝脏主要受这两种病原体的影响。这一结果将加深我们对为什么与工业化国家相比，第三世界(蠕虫流行)国家的乙肝慢性病发病率要高得多的理解。在未来，这可能会对世界范围内的乙肝治疗和疫苗接种工作产生直接影响，目前这些努力忽视了蠕虫合并感染的作用。

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.