Mechanism of DCs Dysfunction in Chronic HBV Infection

Currently, chronic hepatitis B virus (HBV) infection therapies are limited to pegylated interferon alpha (Peg-IFNα) and nucleos(t)ide analogues (NUCs), alone or in combination. Even though they can reduce viremia level (circulating viral load), the loss of HBs antigen (HBsAg), which indicates functional clearance of the virus, is achieved in less than 10% of cases.

The absence of curative treatment to eliminate the infection justifies the need to define new targets and to develop new therapeutic strategies, with an immuno-therapeutic component.

Chronic HBV infection is associated with persistent and virally-induced immune deficiency. The immunological control of the infection seems essential to the functional clearance of the virus. The restoration of appropriate immune responses against the virus could prove to be a promising therapeutic strategy. However, the mechanisms in which HBV modulates immune function is still poorly understood.

Dendritic cells (DCs) have an essential role in immunity. They play a central role in the induction and regulation of immune responses. Also, they play a particularly crucial role in the induction and orientation of antiviral immunity due to their unique properties at the interface between innate and acquired immune responses. In several chronic viral infections, DCs appear defective. The immune responses induced in the early stages of infection seem to be a crucial guide on the progression of the infection into the resolution or the chronicity.

Objective of the investigators is to better understand the virus escape mechanism from immune control, particularly, to determine the mechanisms in which the virus modulates the functions of DCs, crucial for the subsequent orientation of antiviral immune responses, to define the molecular mechanisms of this inhibition and their consequences on the antiviral effectors functions, in order to propose new immunotherapeutic approaches that compromise the chronicity of the infection and treat the infection permanently and definitively.