Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus
Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus
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DOI：
10.1159/000430367
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发表时间：
2015-08
影响因子：
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通讯作者：
Ting Tian;Dandan Sun;Peng Wang;Han-zhi Wang;X. Bai;Xiaofu Yang;Zheng-ping Wang;M. Dong
中科院分区：
文献类型：
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作者：
Ting Tian;Dandan Sun;Peng Wang;Han-zhi Wang;X. Bai;Xiaofu Yang;Zheng-ping Wang;M. Dong
背景资料：大约5%的新生儿通过宫内传播感染了B型肝炎病毒（HBV），但HBV阳性母亲所生的大多数婴儿都受到了保护。然而，避免宫内传播的机制仍然难以捉摸，并且已经提出了Toll样受体（TLR）的作用。本研究的目的是阐明TLR 7和8是否参与预防HBV宫内传播。方法：采用真实的时间聚合酶链反应（PCR）检测胎盘及滋养层细胞中TLR和细胞因子的表达。用小干扰RNA（siRNA）干扰滋养细胞MyD 88的表达。建立了模拟滋养层屏障的体内模型，以评估MyD 88 siRNA对HBV跨滋养层屏障传播的影响。结果如下：对照组（HBV阴性孕妇）、非感染组（HBV阳性孕妇未感染婴儿）和感染组（HBV阳性孕妇感染婴儿）胎盘组织中TLR 7（F = 3.263，P = 0.048）和TLR 8（F=3.257，P=0.048）的表达差异有统计学意义。TLR 7在非感染组的表达显著高于感染组（P=0.039）和对照组（P=0.043）。TLR 8在非感染组与对照组之间的表达差异有统计学意义（P=0.014），在非感染组与感染组之间的表达差异接近但无统计学意义（P=0.074）。滋养细胞经HBV感染后，TLR 7（P<0.001）、TLR 8（P=0.005）、MyD 88（P= 0.004）、IFN-α（P= 0.004）、IFN-β（P<0.001）和IL-8（P=0.001）的表达均显著增加。siRNA干扰MyD 88后，IFN-α（P<0.001）、IFN-β（P=0.01）和IL-8（P<0.001）的表达明显降低，而HBV通过滋养层屏障的转运量明显增加（P=0.03）。结论：滋养层细胞上的TLR 7和TLR 8通过抑制HBV跨滋养层转运，在预防HBV宫内传播中发挥重要作用。
Background: Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission, but most of the infants born to HBV-positive mothers are protected from infection. However, the mechanisms by which intrauterine transmission is avoided remain elusive, and the roles of toll-like receptors (TLRs) have been proposed. The aims of this study were to clarify if TLR 7 and 8 are involved in the prevention of intrauterine transmission of HBV. Methods: Real time polymerase-chain reaction (PCR) was used to determine the expression of TLRs and cytokines in placenta and trophoblasts. The expression of MyD88 was interfered with small interfering RNA (siRNA) in trophoblasts. An in intro model mimicking trophoblast barrier was established to evaluate the effect of MyD88 siRNA on HBV transmission across trophoblast barrier. Results: There were significant differences in placental expression of TLR7 (F=3.263, P=0.048) and TLR8 (F=3.257, P=0.048) among control (HBV-negative women), non-infected group (HBV-positive women whose infants were not infected) and infected group (HBV-positive women whose infants were infected). The expression of TLR7 was significantly higher in non-infected group than infected group (P=0.039) and control (P=0.043). There was a significant difference in TLR8 expression between non-infected group and control (P=0.014), and the difference was close to but not significant (P=0.074) between non-infected and infected groups. Exposure of trophoblast to HBV significantly induced the expression of TLR7 (P<0.001), TLR8 (P=0.005), MyD88 (P=0.004), interferon (IFN)-α (P=0.004), IFN-β (P<0.001) and interleukin (IL)-8 (P=0.001). When MyD88 was interfered by siRNA, the expression of IFN-α (P<0.001), IFN-β (P=0.01) and IL-8 (P<0.001) was significantly decreased while the amount of HBV transcytosed across trophoblastic barrier significantly increased (P=0.03). Conclusions: TLR7 and TLR8 on trophoblastic cells play an important role in the prevention of intrauterine HBV transmission by inhibiting HBV translocation across trophoblast.