Natural killer cell activation contributes to hepatitis B viral control in a mouse model.
Natural killer cell activation contributes to hepatitis B viral control in a mouse model.
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自然杀伤细胞激活有助于小鼠模型中乙型肝炎病毒的控制
DOI：
10.1038/s41598-017-00387-2
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发表时间：
2017-03-22
影响因子：
4.6
通讯作者：
Yin W
中科院分区：
文献类型：
--
作者：
Tong S;Liu G;Li M;Li X;Liu Q;Peng H;Li S;Ren H;Yin W
CD4+T 细胞和 CD8+T 细胞在乙型肝炎病毒 (HBV) 感染中的作用已得到充分证明。然而，先天免疫在乙型肝炎病毒感染中的作用仍不清楚。在这里，我们研究了聚肌苷酸：聚胞苷酸 (PolyI:C) 激活先天免疫对 HBV 感染的影响。通过将pAAV/HBV1.2质粒流体注射到C57BL/6小鼠体内建立慢性HBV复制小鼠模型。我们发现 HBV 似乎并未在小鼠模型中诱导活跃的 NK 细胞反应。早期 PolyI:C 治疗可显着降低血清 HBV 水平并导致 HBV 清除。注射 PolyI:C 后，NK 细胞被激活并在肝脏中积累。 NK 细胞的耗竭显着减弱了 PolyI:C 的抗 HBV 活性。此外，我们发现 NK 细胞产生 IFN-γ 对于模型中 PolyI:C 的抗病毒作用至关重要。重要的是，PolyI:C 激活 NK 细胞还可能导致 HBV 耐受小鼠和 HBV 转基因小鼠的 HBV 抑制。这些结果表明，在自然 HBV 感染期间，活化的 NK 细胞可能会抑制 HBV 并有助于 HBV 清除。此外，NK细胞的治疗性激活可能代表治疗慢性乙型肝炎病毒感染的新策略。
The roles of CD4 + T cells and CD8 + T cells in hepatitis B virus (HBV) infection have been well documented. However, the role of innate immunity in HBV infection remains obscure. Here we examined the effect of activation of innate immunity by polyinosinic: polycytidylic acid (PolyI:C) on HBV infection. A chronic HBV replication mouse model was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. We found that HBV did not seem to induce an active NK-cell response in the mouse model. Early PolyI:C treatment markedly decreased serum HBV levels and led to HBV clearance. Following PolyI:C injection, NK cells were activated and accumulated in the liver. Depletion of NK cells markedly attenuated the anti-HBV activity of PolyI:C. Moreover, we found that IFN-γ production from NK cells was essential for the antiviral effect of PolyI:C in the model. Importantly, activation of NK cells by PolyI:C could also lead to HBV suppression in HBV-tolerant mice and HBV-transgenic mice. These results suggest that activated NK cells might suppress HBV and contribute to HBV clearance during natural HBV infection. In addition, therapeutic activation of NK cells may represent a new strategy for the treatment of chronic HBV infection.