Crosstalk between innate and adaptive immunity in hepatitis B virus infection

Abstract

Hepatitis B virus (HBV) infection is a major public health problem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is responsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.

Keywords: Crosstalk; Hepatitis B virus; Innate immune; Adapative immune

Core tip: Hepatitis B virus (HBV) is poorly sensed by the innate immune system and can escape innate immune recognition at the early stage of infection. HBV-specific T-cell responses are timely and efficiently induced in acute self-limited infections but are deeply exhausted in chronic hepatitis B. The tolerogenic effect of the liver environment and the persistent exposure of T cells to high antigen loads play a key role in the pathogenesis of T-cell inhibition in chronic HBV infection. Combination of reduction of HBV and virus antigen loads and restoration of the anti-viral T-cell function may represent a strategy to cure chronic HBV infections.