Dissecting the dendritic cell controversy in chronic hepatitis B virus infection

Abstract

Therapeutic vaccines to boost endogenous T-cell immunity rely on the stimulatory capacity of dendritic cells (DCs). The functionality of DCs in chronic hepatitis B virus (HBV) infection has been a long-standing debate. Therefore, we have attempted to summarize multiple studies investigating DC function in chronic HBV patients to determine whether common observations can be drawn. We found that the frequency and function of ex vivo-tested myeloid and plasmacytoid DCs were largely intact in patients with HBV infection and similar to those of healthy donor DCs. The main exception was reduced IFN-a production by plasmacytoid DC from chronic HBV patients. This reduced IFN-a production correlated with liver inflammation in multiple studies but not with viral load, suggesting that viral antigens have little effect on DC function. The majority of the confusion about DC function arises from studies reporting the reduced function of healthy donor DCs exposed to various sources of HBV in vitro. These direct effects of viral antigens are in contrast to data from HBV-infected patients. The variations in the assays used and areas that require further investigation are also covered

Hepatitis B Virus Surface Antigen Activates Myeloid Dendritic Cells via a Soluble CD14-Dependent Mechanism

“…Only a limited number of studies addressed the DC phenotype of myeloid DC in CHB patients ex vivo, as reviewed in references 8 and 24. Enhanced mDC maturation in CHB patients compared to healthy control individuals was previously reported by a single study from our group (25), whereas the majority of these studies did not find enhanced DC maturation in CHB patients (8,24). We found a lot of variation between patients, however, and because HBsAg levels were not taken into account in these previous studies, it is possible that the effect on DC maturation may have been overlooked.…”

Cellular and molecular regulation of innate inflammatory responses

“…130 The regulatory capacity of DCs at steady state is programmed by specific local microenvironment, such as stromal cells of the spleen, lung and liver or intestinal epithelial cells. [131][132][133][134][135] Thymic DCs induce Treg-cell development via production of IL-2, 136 and that CD11b( − ) cDCs from the gut-draining lymph nodes were critical for induction of peripheral Treg cells and oral tolerance. 137 The presence of exogenous immunosuppressive mediators, genetic manipulation, specific pathogenic stimuli also induce regulatory property of DCs through various mechanisms.…”

Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

“…Moreover, the use of cells derived from chronically infected patients is best suited to performing more relevant ex vivo experiments. Such experimental drawbacks are often at the origin of controversies regarding the impact of HBV on innate immune cell function in the context of CHB (28). This was well exemplified in the case of CD14 ϩ myeloid dendritic cells (29,30).…”