title: 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.
authors: Women's Hospital, School of Medicine, Zhejiang University, Key Laboratory of Women's Reproductive Health of Zhejiang Province, Key Laboratory of Reproductive Genetics of the Ministry of Education, Hangzhou, China.
authors: Ting
authors: T
authors: Tian
authors: Dandan
authors: D
authors: Sun
authors: Peng
authors: P
authors: Wang
authors: Hanzhi
authors: H
authors: Wang
authors: Xiaoxia
authors: X
authors: Bai
authors: Xiaofu
authors: X
authors: Yang
authors: Zhengping
authors: Z
authors: Wang
authors: Minyue
authors: M
authors: Dong
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D051199:Toll-Like Receptor 7 / Q000235:genetics* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology*
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8