Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota
Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota
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DOI：
10.1073/pnas.1424775112
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发表时间：
2015-02-17
影响因子：
11.1
通讯作者：
Chen, Ding-Shinn
中科院分区：
文献类型：
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作者：
Chou, Han-Hsuan;Chien, Wei-Hung;Chen, Ding-Shinn
人类感染B型肝炎病毒（HBV）的一个独特特征是，病毒清除在很大程度上取决于暴露的年龄。然而，其原因尚不清楚。在这里，我们表明，肠道微生物群有助于HBV免疫力的年龄依赖性在一个流体动力学转染小鼠模型。尽管成年（12周龄）C3 H/HeN小鼠在注射后6周（wpi）内清除了HBV，但它们的年轻（6周龄）小鼠在26 wpi时仍保持HBV阳性。使用抗生素对6至12周龄的肠道微生物群进行灭菌可阻止成年小鼠快速清除HBV。Toll样受体（TLR）4突变（C3 H/HeJ）的年轻小鼠表现出快速的HBV清除。结果表明，在肠道细菌建立之前，通过TLR 4依赖性途径，对HBV的免疫耐受途径在年轻小鼠中占主导地位，成年小鼠肠道微生物群的成熟刺激了肝脏免疫，导致HBV快速清除。
A unique feature of hepatitis B virus (HBV) infection in humans is that viral clearance heavily depends on the age of exposure. However, the reason for this remains unclear. Here we show that gut microbiota contribute to the age dependence of HBV immunity in a hydrodynamic transfection mouse model. Although adult (12-wk-old) C3H/HeN mice cleared HBV within 6 wk postinjection (wpi), their young (6-wk-old) counterparts remained HBV-positive at 26 wpi. Sterilization of gut microbiota from 6 to 12 wk of age using antibiotics prevented adult mice from rapidly clearing HBV. Young mice with the Toll-like-receptor (TLR) 4 mutation (C3H/HeJ) exhibited rapid HBV clearance. The results suggest that an immuno-tolerating pathway to HBV prevailed in young mice, before the establishment of gut bacteria, through a TLR4-dependent pathway and that the maturation of gut microbiota in adult mice stimulated liver immunity, resulting in rapid HBV clearance.