Objectives: HBV infection typically leads to chronic hepatitis in newborns and some adults with weakened immune systems. The mechanisms by which virus escapes immunity remain undefined. Regulatory dendritic cells (DCregs) contributing to immune escape have been described. We wondered whether or not HBeAg as an immunomodulatory protein could induce DCreg which might subsequently result into HBV persistence.
Methods: The immunophenotyping, T-cell activation and cytokine production were analyzed in HBeAg-treated DCs from normal or cyclophosphamide (Cy)-induced immunocompromised mice.
Results: HBeAg tended to promote bone marrow derived DCs (BMDCs) from Cy-treated mice into CD11b(high)PIR-B(+) regulatory DCs exhibiting the lowest T-cell stimulatory capacity and interleukin (IL)-12p70 production compared with controls. Neutralization of IL-10 significantly inhibited the regulatory effect of these DCs on T-cell stimulation of mature DCs. After lipopolysaccharides (LPS) stimulation, marked phosphorylation of Akt was detected in HBeAg treated DCs from immunocompromised mice. Blocking the PI3K-Akt pathway by LY294002 led to an enhancement of IL-12 production. PI3K signalling pathway appears to be involved in the decreased IL-12 secretion by HBeAg treated DCs.
Conclusions: These findings suggest that HBeAg may program the generation of a new DC subset with regulatory capacity under the condition of immunosuppression, which may presumably contribute to the persistent HBV infection.
Keywords: Cell differentiation; Chronic hepatitis B; HBeAg; Immune regulation; Regulatory dendritic cells.
Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.