Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B
Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B
复制标题
DOI：
10.1172/jci68182
复制
发表时间：
2013-09-01
影响因子：
15.9
通讯作者：
Baron, Jody L.
中科院分区：
文献类型：
--
作者：
Publicover, Jean;Gaggar, Anuj;Baron, Jody L.
乙型肝炎病毒（HBV）是引起免疫介导性肝炎的主要人类病原体。对HBV的成功免疫取决于年龄：病毒清除发生在大多数成年人中，而新生儿和幼儿通常会发生慢性感染。利用小鼠HBV感染模型，我们寻找支持HBV年龄依赖性结果的机制，并证明肝巨噬细胞促进成人肝脏内的淋巴组织和免疫启动，并促进成功的免疫。相比之下，淋巴组织和免疫启动在年轻小鼠和巨噬细胞缺失的成年小鼠的肝脏中大大减少，导致HBV免疫丧失。此外，我们发现参与B淋巴细胞运输和淋巴样结构和发育的CXCL13在成年小鼠和人肝巨噬细胞中以年龄依赖的方式表达，并在促进有效的HBV免疫应答中发挥不可或缺的作用。综上所述，这些结果确定了有效控制HBV所需的一些免疫机制。
Hepatitis B virus (HBV) is a major human pathogen that causes immune-mediated hepatitis. Successful immunity to HBV is age dependent: viral clearance occurs in most adults, whereas neonates and young children usually develop chronic infection. Using a mouse model of HBV infection, we sought mechanisms underpinning the age-dependent outcome of HBV and demonstrated that hepatic macrophages facilitate lymphoid organization and immune priming within the adult liver and promote successful immunity. In contrast, lymphoid organization and immune priming was greatly diminished in the livers of young mice, and of macrophage-depleted adult mice, leading to abrogated HBV immunity. Furthermore, we found that CXCL13, which is involved in B lymphocyte trafficking and lymphoid architecture and development, is expressed in an age-dependent manner in both adult mouse and human hepatic macrophages and plays an integral role in facilitating an effective immune response against HBV. Taken together, these results identify some of the immunological mechanisms necessary for effective control of HBV.