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We hypothesize that subclinical viral infections of the placenta are a factor sensitizing women to intrauterine bacterial infection. Specifically, we propose that viral\u2010induced placental <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 inhibition results in a robust inflammatory response to low concentrations of bacteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human trophoblast <jats:styled-content style=\"fixed-case\">SW<\/jats:styled-content>.71, C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6, and interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>) receptor knockout animals were used to determine <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> function. Illumina and Bio\u2010Rad microarrays identified pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibiting the <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 pathway resulted in a significant increase in inflammatory cytokines such as <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101B in response to <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>. Twist was positively correlated with <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 expression and <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 phosphorylation and overexpressing Twist reduced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101B. Treating <jats:styled-content style=\"fixed-case\">IFNAR<\/jats:styled-content>\u2212\/\u2212 mice with low\u2010dose <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> at E15.5 caused preterm birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 was identified as a key modulator of placental inflammation and, importantly, is commonly affected by viruses. We propose dysregulation of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 is a major determinant for preterm birth associated with polymicrobial infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12501","type":"journal-article","created":{"date-parts":[[2016,2,20]],"date-time":"2016-02-20T14:27:52Z","timestamp":1455978472000},"page":"451-460","source":"Crossref","is-referenced-by-count":66,"title":["Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection\u2010Induced Preterm Birth"],"prefix":"10.1111","volume":"75","author":[{"given":"Karen","family":"Racicot","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine New Haven CT USA"},{"name":"Department of OB\/GYN College of Human Medicine Michigan State University Grand Rapids MI 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