About the Section
The research interests of the Immunology Section are innate and adaptive immune responses to persistent viral infections, in particular those that affect the liver. Much of the work is conducted with blood and liver biopsy samples from clinically well-characterized patients who are followed and treated in the Liver Diseases Branch under IRB-approved protocols. Basic immunological and virological questions that arise from these translational studies are then investigated in suitable model systems. For example, the section is currently using a mouse model of acute and chronic hepatitis that is caused infection with the lymphocytic choriomeningitis virus to study basic mechanisms of immune regulation and tolerance. In addition, in vitro models of viral infection are being used to investigate how innate immune cells sense infected cells.
Much of the work has focussed on hepatitis B virus (HBV) and hepatitis B virus (HCV) infection, which affect about 500 million people worldwide. The spectrum of disease ranges from acute to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Although HBV infection can be prevented by a vaccine, there is still no curative treatment for those who are already chronically infected. This is because antiviral agents do not eliminate the transcriptional template of HBV, the covalently closed circular DNA. For HCV, a vaccine has not yet been developed.
A major emphasis of the research program has been the identification of innate and adaptive immune response that mediate viral clearance and the analysis of mechanisms of viral immune evasion. An equally important issue is the role of innate and adaptive immune responses in chronic viral hepatitis and disease progression because the incidence of complications from chronic liver disease, such as cirrhosis and hepatocellular carcinoma, is projected to increase over the next 20 years. The section is therefore evaluating strategies for immune modulation and immunotherapy.
The long-term goal of this program is the development of vaccines to prevent infections and immunotherapies to modulate the progression of chronic liver disease.
The research will help decrease the burden of liver disease and in particular chronic viral hepatitis and the long-term consequences of chronic inflammation of the liver such as cancer. In addition, the basic immunological mechanisms that are being studied are relevant for other diseases, for example for immune responses against other pathogens and tumors and for autoimmune diseases.