Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus

Abstract

Summary Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV‐infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood‐derived mDC of healthy controls also actively take up HBsAg in a time‐dependent manner. Cytokine‐induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up‐regulation of costimulatory molecules and a decreased T‐cell stimulatory capacity, as assessed by T‐cell proliferation and interferon‐γ production. In addition, the presence of HBV significantly reduced interleukin‐12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity.

Host–virus interactions in hepatitis B and hepatitis C infection

“…Regarding the mechanisms, HBsAg is the causal factor for such disruption of the pDCs, partly by upregulating suppressor molecule SOCS-1 [41]. The dysfunction of myeloid DCs (mDCs) has also been observed, presumably due to HBV particles and HBsAg [43]. The functional impairment of NK cells and DCs in chronic HBV infection might be actively involved in viral persistency.…”

Role of Tim-3 in hepatitis B virus infection: An overview

“…In particular, DCs control HBV recognition in vivo. Accumulating evidence has demonstrated that compared to DCs from healthy controls, DCs from patients infected with HBV exhibit impaired function [52,53] , yet the reasons for this impairment remain unclear. Researchers have focused on developing a curative DC vaccine that activates the immune response through rescuing the function of DCs to treat HBV.…”

Dissecting the dendritic cell controversy in chronic hepatitis B virus infection

“…All of the studies report a reduction in costimulatory molecule expression following HBV exposure. 21,23,31,32 However, different antigens or virions regulated the expression of different receptors. Similarly, most studies have found cytokine production to be impaired following exposure to HBV or HBV antigens; however, similar to the phenotype experiments, different forms of the antigen had different effects (Table 4).…”