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Both systemic infection and bacterial ascension through the vagina\/cervix to the amniotic cavity are strongly associated with PTB. However, the contribution of maternal or fetal inflammatory responses in the context of systemic or localized models of infection-driven PTB is not well defined. Here, using intraperitoneal or intraamniotic LPS challenge, we examined the necessity and sufficiency of maternal and fetal Toll-like receptor (TLR) 4 signaling in induction of inflammatory vigor and PTB. Both systemic and local LPS challenge promoted induction of inflammatory pathways in uteroplacental tissues and induced PTB. Restriction of TLR4 expression to the maternal compartment was sufficient for induction of LPS-driven PTB in either systemic or intraamniotic challenge models. In contrast, restriction of TLR4 expression to the fetal compartment failed to induce LPS-driven PTB. Vav1-Cre\u2013mediated genetic deletion of TLR4 suggested a critical role for maternal immune cells in inflammation-driven PTB. Further, passive transfer of WT in vitro\u2013derived macrophages and dendritic cells to TLR4-null gravid females was sufficient to induce an inflammatory response and drive PTB. Cumulatively, these findings highlight the critical role for maternal regulation of inflammatory cues in induction of inflammation-driven parturition.<\/jats:p>","DOI":"10.1172\/jci.insight.138812","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T11:02:14Z","timestamp":1605697334000},"source":"Crossref","is-referenced-by-count":36,"title":["Maternal regulation of inflammatory cues is required for induction of preterm birth"],"prefix":"10.1172","volume":"5","author":[{"given":"Monica","family":"Cappelletti","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA."},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-801X","authenticated-orcid":true,"given":"Jessica 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