{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:04:37Z","timestamp":1789448677446,"version":"build-2803163510"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"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":[[2009,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pregnancy outcome is severely compromised by intrauterine infections and inflammation. Although the pregnant uterine microenvironment is replete with innate immune cells and TLR expression, the mechanisms that facilitate adverse effects of their activation are largely unknown. In this study, we mimic the activation of TLR9 with its pathogenic ligand hypomethylated CpG and demonstrate that IL-10 proficiency protects against CpG-induced pregnancy complications. We show that fetal resorption and preterm birth are rapidly induced in IL-10\u2212\/\u2212 mice by low doses of CpG (\u223c25 \u03bcg\/mouse) when injected i.p. on gestational day 6 or gestational day 14, respectively. In contrast, wild-type mice failed to experience such effects at comparable doses, but pups born at term displayed craniofacial\/limb defects in response to higher doses (\u223c400 \u03bcg\/mouse). Pregnancy complications in IL-10\u2212\/\u2212 mice were associated with unexpected and robust TLR9-triggered activation and amplification of uterine neutrophil and macrophage subpopulations followed by their migration to the placental zone. Furthermore, a dramatic increase in serum levels of mouse KC and TNF-\u03b1 production by uterine F4\/80+ cells, but not uterine NK or Gr-1+CD11b+ cells, was observed. Depletion of F4\/80+ macrophages or neutralization of TNF-\u03b1 rescued pregnancy to term. Our results have important implications for IL-10-mediated \u201cuterine tolerance\u201d against CpG-driven innate immune activation.<\/jats:p>","DOI":"10.4049\/jimmunol.0900788","type":"journal-article","created":{"date-parts":[[2009,6,26]],"date-time":"2009-06-26T20:49:03Z","timestamp":1246049343000},"page":"1144-1154","source":"Crossref","is-referenced-by-count":155,"title":["TLR9 Activation Coupled to IL-10 Deficiency Induces Adverse Pregnancy Outcomes"],"prefix":"10.1093","volume":"183","author":[{"given":"Jessica E","family":"Thaxton","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University , Providence, RI 02905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Romero","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health\/Department of Health and Human Services , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University , Providence, RI 02905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,15]]},"reference":[{"key":"2026012811283374300_R1","first-page":"1500","article-title":"Intrauterine infection and preterm delivery.","volume-title":"N. 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