The Effect of Chronic Hepatitis B Virus Infection on BDCA3+Dendritic Cell Frequency and Function

Chronic hepatitis B virus (HBV) infection results from inadequate HBV-specific immunity. BDCA3(+) dendritic cells (DCs) are professional antigen presenting cells considered to be important for antiviral responses because of specific characteristics, including high interferon-lambda production. BDCA3+ DCs may thus also have a role in the immune response against HBV, and immunotherapeutic strategies aiming to activate DCs, including BDCA3(+) DCs, in patient livers may represent an interesting treatment option for chronic HBV. However, neither the effect of chronic hepatitis B (CHB) infection on the frequency and function of BDCA3(+) DCs in liver and blood, nor the effect of the viral surface protein (HBsAg) that is abundantly present in blood of infected individuals are known. Here, we provide an overview of BDCA3(+) DC frequency and functional capacity in CHB patients. We find that intrahepatic BDCA3(+) DC numbers are increased in CHB patients. BDCA3(+) DCs from patient blood are not more mature at steady state, but display an impaired capacity to mature and to produce interferon-lambda upon polyI: C stimulation. Furthermore, in vitro experiments exposing blood and intrahepatic BDCA3(+) DCs to the viral envelope protein HBsAg demonstrate that HBsAg does not directly induce phenotypical maturation of BDCA3(+) DCs, but may reduce IFN-lambda production via an indirect unknown mechanism. These results suggest that BDCA3(+) DCs are available in the blood and on site in HBV infected livers, but measures may need to be taken to revive their function for DC-targeted therapy.