Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission.
Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission.
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DOI：
10.1016/j.immuni.2016.04.008
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发表时间：
2016-05-17
期刊：
影响因子：
32.4
通讯作者：
Ou JH
中科院分区：
文献类型：
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作者：
Tian Y;Kuo CF;Akbari O;Ou JH
与成人之间的B型肝炎病毒（HBV）水平传播（通常导致自限性急性感染）相反，HBV从母亲到儿童的垂直传播（通常导致慢性感染）。然而，垂直传播与慢性感染之间的联系机制尚不清楚。我们开发了一种小鼠模型来研究母亲HBV感染对后代HBV持续性的影响，发现母亲携带的HBV损害了后代对HBV的CD 8 + T细胞应答，导致HBV持续性。这种CD 8 + T细胞应答的损害是由肝巨噬细胞介导的，这些巨噬细胞易受母体HBV e抗原（HBeAg）的影响，通过上调抑制性配体PD-L1和改变HBeAg再刺激后的极化来支持HBV持续存在。肝脏巨噬细胞的消耗导致后代中CD 8 + T细胞活化和HBV清除，提高了靶向巨噬细胞治疗慢性HBV患者的可能性。
In 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.