Xu Yongfen, Hu Yunwen, Shi Bisheng, Zhang Xiaonan, Wang Jiefei, Zhang Zhanqing, Shen Fang, Zhang Qin, Sun Shuhui, Yuan Zhenghong
Fudan University, China.
Mol Immunol. 2009 Aug;46(13):2640-6. doi: 10.1016/j.molimm.2009.04.031. Epub 2009 Jun 5.
Plasmacytoid dendritic cells (pDCs), the professional producers of type I interferons (IFN-alpha/beta), play a pivotal role in innate and adaptive immune responses against viral infections. Although functional impairment of circulating pDCs in chronic hepatitis B (CHB) patients has been reported previously, the mechanism responsible for these defects remains unclear. We hypothesize that HBsAg circulating in high amounts during HBV infection may interact with pDC and contribute to pDC dysfunction. In support of this hypothesis we show that pDCs treated with HBsAg secreted much less IFN-alpha than control pDCs. Furthermore, suppression is specific for TLR9, with no effects upon TLR7-mediated IFN-alpha secretion. HBsAg inhibited TLR9-mediated IRF-7 expression and nuclear translocation, which are important for induction of IFN-alpha gene transcription. HBsAg upregulated the SOCS-1 expression and bound to BDCA-2 receptors on the plasma membrane of pDCs, resulting in the inhibition of the IFN-alpha production. In conclusion, the above data suggested that HBsAg may directly interfere with the function of pDC through HBsAg-mediated upregulation of SOCS-1 expression and BDCA-2 ligation, which could partially explain how HBV evades the immune system to establish a persistent infection.
浆细胞样树突状细胞（pDC）是I型干扰素（IFN-α/β）的主要产生细胞，在针对病毒感染的固有免疫和适应性免疫反应中起关键作用。尽管先前已有报道慢性乙型肝炎（CHB）患者循环pDC功能受损，但其缺陷的机制仍不清楚。我们推测，HBV感染期间大量循环的HBsAg可能与pDC相互作用并导致pDC功能障碍。支持这一假设的是，我们发现用HBsAg处理的pDC分泌的IFN-α比对照pDC少得多。此外，这种抑制作用对TLR9具有特异性，对TLR7介导的IFN-α分泌没有影响。HBsAg抑制TLR9介导的IRF-7表达和核转位，这对IFN-α基因转录的诱导很重要。HBsAg上调SOCS-1表达并与pDC质膜上的BDCA-2受体结合，导致IFN-α产生受到抑制。总之，上述数据表明，HBsAg可能通过HBsAg介导的SOCS-1表达上调和BDCA-2连接直接干扰pDC的功能，这可以部分解释HBV如何逃避免疫系统以建立持续感染。
