Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission

• Developed a mouse model to study effect of maternal HBV on persistence in offspring
• The CTL response to HBV is impaired in the offspring of HBV-positive mothers
• Depletion of macrophages in offspring restores the CTL response for HBV clearance
• Maternal HBeAg enhances PD-L1 expression in macrophages of offspring to suppress CTLs

SummaryIn contrast to horizontal transmission of hepatitis B virus (HBV) between adults, which often leads to self-limited acute infection, vertical transmission of HBV from mother to child often leads to chronic infection. However, the mechanisms linking vertical transmission with chronic infection are not known. We developed a mouse model to study the effect of maternal HBV infection on HBV persistence in offspring and found that HBV carried by the mother impaired CD8+ T cell responses to HBV in her offspring, resulting in HBV persistence. This impairment of CD8+ T cell responses was mediated by hepatic macrophages, which were predisposed by maternal HBV e antigen (HBeAg) to support HBV persistence by upregulation of inhibitory ligand PD-L1 and altered polarization upon restimulation with HBeAg. Depletion of hepatic macrophages led to CD8+ T cell activation and HBV clearance in the offspring, raising the possibility of targeting macrophages to treat chronic HBV patients.

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