title: Differential effects of the CpG-Toll-like receptor 9 axis on pregnancy outcome in nonobese diabetic mice and wild-type controls.
abstract: OBJECTIVE
  To elucidate the relationship between CpG-induced activation of innate immunity and pregnancy outcome.
  
  
  METHODS
  An animal model-based study.
  
  
  METHODS
  Academic.
  
  
  METHODS
  Pregnant nonobese diabetic (NOD) mice were compared with nonimmunodeficient mice.
  
  
  METHODS
  We mimic toll-like receptor 9 (TLR9) activation using CpG ODN administration in pregnant wild-type (WT) and natural killer (NK) cell-deficient NOD mice.
  
  
  METHODS
  Evaluation of fetal resorption and preterm birth in pregnant mice; flow-cytometric analysis and ELISA detection.
  
  
  RESULTS
  CpG-induced fetal resorption or preterm birth was observed steadily only in NOD mice but not in WT mice. Concurrently, CpG treatment triggered amplification of uterine macrophages and neutrophils. Moreover, CpG induced a substantial increase of serum mouse keratinocyte-derived cytokine (mKC) and tumor necrosis factor-α (TNF-α) that were produced by uterine CD11b(+)F4/80(+) cells but not by NK or CD11b(+)Gr-1(+) cells. In addition, depletion of F4/80(+) cells abrogated a CpG-induced increase in TNF-α production and improved pregnancy outcomes in NOD mice treated with CpG.
  
  
  CONCLUSIONS
  These results provide evidence that CpG-driven innate immune activation may lead to activation and amplification of macrophages followed by their migration to fetomaternal microenvironment, up-regulated TNF-α production, and consequent adverse pregnancy outcomes.
authors: Department of Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Yun
authors: Y
authors: Sun
authors: Xiaoli
authors: X
authors: Qin
authors: Bin
authors: B
authors: Shan
authors: Wenjing
authors: W
authors: Wang
authors: Qinling
authors: Q
authors: Zhu
authors: Surendra
authors: S
authors: Sharma
authors: Ji
authors: J
authors: Wu
authors: Yi
authors: Y
authors: Lin
mesh_terms: D000818:Animals; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009838:Oligodeoxyribonucleotides / Q000633:toxicity*; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000139:chemically induced / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000502:physiology*
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9