title: Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth.
abstract: OBJECTIVE
  Preterm birth (PTB) affects approximately 12% of pregnancies and at least 50% of cases have no known risk factors. We hypothesize that subclinical viral infections of the placenta are a factor sensitizing women to intrauterine bacterial infection. Specifically, we propose that viral-induced placental IFN-β inhibition results in a robust inflammatory response to low concentrations of bacteria.
  
  
  METHODS
  Human trophoblast SW.71, C57BL/6, and interferon (IFN) receptor knockout animals were used to determine IFN function. Illumina and Bio-Rad microarrays identified pathways.
  
  
  RESULTS
  Inhibiting the IFN-β pathway resulted in a significant increase in inflammatory cytokines such as IL-1B in response to LPS. Twist was positively correlated with IFN-β expression and STAT3 phosphorylation and overexpressing Twist reduced IL-1B. Treating IFNAR-/- mice with low-dose LPS at E15.5 caused preterm birth.
  
  
  CONCLUSIONS
  IFN-β was identified as a key modulator of placental inflammation and, importantly, is commonly affected by viruses. We propose dysregulation of IFN-β is a major determinant for preterm birth associated with polymicrobial infection.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.|Department of OB/GYN, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Racicot
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.|Department of OB/GYN, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Paulomi
authors.initials: P
authors.lastname: Aldo
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Vikki
authors.initials: V
authors.lastname: Abrahams
authors.affiliation: Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Guindy
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, Detroit, MI, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D047928:Premature Birth / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: C507964:IFNAR1 protein, human; C508585:IL1B protein, human; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta
keywords: Bacteria; infection; interferon; polymicrobial; pregnancy; trophoblast; virus