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Dendritic cells and chronic hepatitis virus carriers
1Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Insights
Dendritic cells (DCs) are crucial for initiating immune responses against hepatitis B virus (HBV) and hepatitis C virus (HCV). Understanding DC function in chronic infections may reveal new therapeutic strategies for millions of carriers worldwide.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections affect over 400 million people globally.
- These chronic infections can lead to severe liver diseases, including cirrhosis and hepatocellular carcinoma.
- The exact mechanisms of chronic infection development are unclear, but host immune response defects are implicated.
Purpose of the Study:
- To review the role of dendritic cells (DCs) in the pathogenesis of chronic hepatitis B and C.
- To summarize current knowledge on hepatitis virus carrier states and DC properties.
- To discuss DC phenotypes, functions, and therapeutic potential in HBV and HCV infection models.
Main Methods:
- Review of existing literature on DC biology and hepatitis virus pathogenesis.
- Analysis of data on DC phenotypes and functions in human and animal models of chronic HBV and HCV.
- Examination of vaccine therapy outcomes in HBV transgenic mouse models.
Main Results:
- DCs are critical antigen-presenting cells involved in initiating and regulating immune responses.
- Dysfunctional DCs may contribute to the inability to clear HBV and HCV, leading to chronic infection.
- Vaccine-induced DC activation in a mouse model led to clearance of viral antigens and reduced viral DNA.
Conclusions:
- Dendritic cells play a pivotal role in the immune response to HBV and HCV.
- Defective DC function is a potential driver of chronic hepatitis virus infections.
- Targeting DCs offers a promising avenue for developing novel therapies for chronic hepatitis B and C.
Abstract:
Many individuals infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) are unable to clear these viruses following an acute infection and become chronically infected. There are more than 400 million HBV and HCV carriers in the world and a considerable number of these patients would eventually develop more severe complications like liver cirrhosis and hepatocellular carcinoma. It is not clearly known how an individual develops a chronic hepatitis virus carrier state; however, a defective immune response of the host is thought to play a critical role in the underlying pathogenetic mechanism. On the other hand, dendritic cells (DCs), the most potent antigen-presenting cells, are widely distributed in both lymphoid and nonlymphoid tissues. Recognition of the microbes or microbial antigens by DCs is one of critical events for the initiation of an immune response. DCs also play a cardinal role during the progression and termination of an immune response. The aim of this overview is to provide information regarding the role of DCs in the pathogenesis of chronic hepatitis due to HBV and HCV in humans and in animal models of HBV and HCV carrier states. First, we summarize our current understanding of the pathogenesis of hepatitis virus carrier states and also of general properties of DCs. Next, we discuss the data on the phenotypes and functions of DCs in both human and murine HBV and HCV carriers. We also discuss vaccine therapy in murine HBV carriers because activation of DCs due to vaccination-initiated HBsAg-specific immune responses in HBV transgenic mice (HBV-Tg), which in turn resulted in complete clearance of hepatitis B surface antigen and hepatitis B e antigen and decreased levels of HBV DNA in some HBV-Tg. Finally, we discuss the extracted questions and future research directions.