Impact of HBeAg on the maturation and function of dendritic cells. (May 2016)

• Record Type: Journal Article
• Authors: Lan, Songsong; Wu, Lecan; Wang, Xiuyan; Wu, Jinming; Lin, Xianfan; Wu, Wenzhi; Huang, Zhiming
• Is Part Of: International journal of infectious diseases. Volume 46(2016:May)
• Page Start: 42
• Page End: 48
• Publication Date: 2016-05
• Subjects: HBeAg -- Regulatory dendritic cells -- Cell differentiation -- Immune regulation -- Chronic hepatitis B; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2016.03.024
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: HBeAg may program the generation of a new type of DC subset with regulatory capacity. DCs from Cy-treated mice exposed to HBeAg exhibited high expression of CD11b and PIR-B. The CD11b high PIR-B + regulatory DCs showed a decreased T-cell stimulatory capacity. The CD11b high PIR-B + regulatory DCs showed a suppressed production of IL-12. Abstract: 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.