Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

Abstract

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.