{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T13:55:45Z","timestamp":1792936545615,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-\u03baB, shown by I\u03baB\u03b1 degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 \u03bcg\/dam) on gestational day 10\u201314. In contrast, TLR9\u2212\/\u2212 mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.<\/jats:p>","DOI":"10.4049\/jimmunol.1103454","type":"journal-article","created":{"date-parts":[[2012,4,29]],"date-time":"2012-04-29T00:15:20Z","timestamp":1335658520000},"page":"5706-5712","source":"Crossref","is-referenced-by-count":160,"title":["TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia"],"prefix":"10.1093","volume":"188","author":[{"given":"Andrea","family":"Scharfe-Nugent","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin\u00e9ad C","family":"Corr","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Keogh","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trinity College Dublin and Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trinity College Dublin and Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Daly","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trinity College Dublin and Coombe Women & Infants University Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A J","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,6,1]]},"reference":[{"key":"2025032410122321800_r1","first-page":"528","article-title":"Changing prognosis for very low birth weight infants","volume":"74","author":"Ehrenhaft","year":"1989","journal-title":"Obstet. 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