State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310031, China.
Inflamm Res. 2012 Sep;61(9):997-1004. doi: 10.1007/s00011-012-0493-z. Epub 2012 Jun 10.
To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection.
Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit.
Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV.
Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs.
研究 Toll 样受体（TLR）7 和 TLR9 介导的浆细胞样树突状细胞（pDC）产生的干扰素 α（IFN-α）在慢性乙型肝炎病毒（HBV）感染患者中是否受损。
从 32 例慢性 HBV 患者和 13 例健康志愿者中制备外周血单核细胞（PBMC），并用洛索核糖或胞苷磷酸鸟苷（CpG）寡脱氧核苷酸（ODN）处理。通过夹心 ELISA 测定上清液中的 IFN-α。通过流式细胞术定量测定 pDC 频率以及 pDC 中 TLR7 和 TLR9 的表达水平。使用高灵敏度实时 PCR 试剂盒定量测定 HBV 的血清病毒载量。
与健康对照组的细胞相比，HBV 组的 PBMC 和 pDC 对 TLR7（洛索核糖）和 TLR9（CpG ODN）配体的 IFN-α产生明显减少（P < 0.05）。从机制上讲，HBV 组外周血中 pDC 的数量以及与 pDC 相关的 TLR7 和 TLR9 的表达明显低于健康对照组（P < 0.05）。此外，pDC 的数量和 pDC 上 TLR9 的表达与 HBV 血清负荷呈负相关。
pDC 产生 IFN-α的受损可能导致慢性 HBV 感染的免疫发病机制，这可能是由于 pDC 数量减少以及 pDC 上 TLR7 和 TLR9 的表达降低所致。
