Tian Yongjun, Kuo Cheng-Fu, Akbari Omid, Ou Jing-Hsiung James
Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Immunity. 2016 May 17;44(5):1204-14. doi: 10.1016/j.immuni.2016.04.008. Epub 2016 May 3.
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.
与成人之间乙肝病毒（HBV）的水平传播往往导致自限性急性感染不同，HBV从母亲垂直传播给孩子往往导致慢性感染。然而，垂直传播与慢性感染之间的关联机制尚不清楚。我们建立了一个小鼠模型来研究母体HBV感染对后代中HBV持续存在的影响，发现母亲携带的HBV损害了其后代CD8(+) T细胞对HBV的反应，导致HBV持续存在。CD8(+) T细胞反应的这种损害由肝巨噬细胞介导，母体HBV e抗原（HBeAg）使肝巨噬细胞易于通过上调抑制性配体PD-L1来支持HBV持续存在，并在受到HBeAg再次刺激时改变极化状态。肝巨噬细胞的清除导致后代中CD8(+) T细胞活化和HBV清除，这增加了将巨噬细胞作为治疗慢性HBV患者靶点的可能性。
