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Updated: Aug 22, 2025
Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
Cholesterol accumulation on dendritic cells reverses chronic hepatitis B virus infection-induced dysfunction
Huajun Zhao1, Yating Yu1, Yucan Wang1
1Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, 250012, China.
Insights
Chronic hepatitis B (CHB) reduces cholesterol in dendritic cells (DCs), impairing immune response. Restoring cholesterol with statins enhances vaccine efficacy against hepatitis B virus (HBV) infection.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Chronic hepatitis B (CHB) is a global health concern with unclear links to cholesterol metabolism.
- Dendritic cells (DCs) play a crucial role in immune responses, but their function in CHB is not fully understood.
Purpose of the Study:
- To investigate the impact of CHB on cholesterol levels and DC function.
- To evaluate the potential of statins to restore DC function and enhance HBV vaccine efficacy.
Main Methods:
- Analysis of free cholesterol, lipid rafts, and metabolic pathways in human and mouse models of CHB.
- Assessment of dendritic cell antigen presentation and immune cell responses in HBV-carrier mice treated with a recombinant HBV vaccine and statins.
Main Results:
- CHB was associated with reduced free cholesterol and impaired lipid raft formation in DCs.
- Statin administration promoted cholesterol accumulation in DCs, restoring lipid rafts and enhancing antigen presentation.
- Cholesterol restoration improved vaccine-mediated elimination of HBV DNA/RNA and HBcAg, boosted HBV-specific CD8+ T cell responses, and promoted memory development and seroconversion.
Conclusions:
- Cholesterol levels are critical for DC function in CHB.
- Strategies targeting cholesterol accumulation in DCs may improve therapeutic vaccine efficacy for CHB.
Abstract:
Chronic hepatitis B (CHB) infection remains a serious public health problem worldwide; however, the relationship between cholesterol levels and CHB remains unclear. We isolated peripheral blood mononuclear cells from healthy blood donors and CHB patients to analyze free cholesterol levels, lipid raft formation, and cholesterol metabolism-related pathways. Hepatitis B virus (HBV)-carrier mice were generated and used to confirm changes in cholesterol metabolism and cell-surface lipid raft formation in dendritic cells (DCs) in the context of CHB. Additionally, HBV-carrier mice were immunized with a recombinant HBV vaccine (rHBVvac) combined with lipophilic statins and evaluated for vaccine efficacy against HBV. Serum samples were analyzed for HBsAg, anti-HBs, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg. CHB reduced free cholesterol levels and suppressed lipid raft formation on DCs in patients with CHB and HBV-carrier mice, whereas administration of lipophilic statins promoted free cholesterol accumulation and restored lipid rafts on DCs accompanied by an enhanced antigen-presentation ability in vitro and in vivo. Cholesterol accumulation on DCs improved the rHBVvac-mediated elimination of serum HBV DNA and intrahepatic HBV DNA, HBV RNA, and HBcAg and promoted the rHBVvac-mediated generation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells, induction of the development of memory responses against HBV reinfection, and seroconversion from HBsAg to anti-HBs. The results demonstrated the important role of cholesterol levels in DC dysfunction during CHB, suggesting that strategies to increase cholesterol accumulation on DCs might enhance therapeutic vaccine efficacy against HBV and support development toward clinical CHB treatment.
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