Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9
Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9
复制标题
慢性乙型肝炎感染患者浆细胞样树突状细胞缺乏，TLR9表达减少
DOI：
10.1016/j.micinf.2009.02.008
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发表时间：
2009-04-01
影响因子：
5.8
通讯作者：
Bao, Shisan
中科院分区：
文献类型：
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作者：
Xie, Qing;Shen, Huai-Cheng;Bao, Shisan
慢性B型肝炎病毒（HBV）感染是一种复制型非细胞病变病毒与宿主抗病毒免疫失调之间的复杂相互作用。浆细胞样树突状细胞（pDC）通过分泌I型干扰素参与先天性抗病毒免疫。Toll样受体（TLR）9参与pDC中表达的主要患者识别受体。使用流式细胞术测定外周血单核细胞（PBMC）中pDC和TLR 9表达的频率。在有/没有pDC的情况下，在胞苷磷酸鸟苷（CpG）的存在下体外评估PBMC的IFN-α产生。还评估了TLR 9、pDC频率和病毒载量之间的相关性。与健康对照相比，慢性HBV患者中pDC中的TLR 9表达显著降低（类似于50%），由TLR 9 mRNA的类似于70%的降低支持，这与体外IFN-α产生的损害相关。此外，这些患者中的pDC频率显著降低（类似于30%），与血清ALT水平和HBV病毒载量负相关。免疫组化法检测慢性HBV患者pDC中HBsAg和HBcAg的表达。我们的结论是，HBV感染导致循环pDC的频率降低，并通过抑制TLR 9的表达而损害其功能。这些数据可为慢性HBV感染的基础研究和临床治疗提供有用的信息。(C)2009年Elsevier Masson SAS。All rights reserved.
Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major patient recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-alpha production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly (similar to 50%) reduced, Supported by similar to 70% reduction or TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-alpha production in vitro. Furthermore, pDCs frequency in these patients was Substantially reduced (similar to 30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection. (C) 2009 Elsevier Masson SAS. All rights reserved.