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To define the immunological signature of the human placenta, we performed unbiased profiling of secreted immune factors from human chorionic villi isolated from placentas at mid and late stages of pregnancy. We show that placental trophoblasts constitutively secrete the inflammasome-associated cytokines IL-1\u03b2 and IL-18, which is blocked by NLRP3 inflammasome inhibitors and occurs without detectable gasdermin D cleavage. We further show that placenta-derived IL-1\u03b2 primes monocytes for inflammasome induction to protect against Listeria monocytogenes infection. Last, we show that the human placenta responds to L. monocytogenes infection through additional inflammasome activation and that inhibition of this pathway sensitizes villi to infection. Our results thus identify the inflammasome as an important mechanism by which the human placenta regulates systemic and local immunity during pregnancy to defend against L. monocytogenes infection.<\/jats:p>","DOI":"10.1084\/jem.20200649","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T13:14:41Z","timestamp":1601039681000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Inflammasome signaling in human placental trophoblasts regulates immune defense against <i>Listeria monocytogenes<\/i> infection"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-3908","authenticated-orcid":true,"given":"Christina","family":"Megli","sequence":"first","affiliation":[{"name":"Division of Maternal-Fetal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 1"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical School, Pittsburgh, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2273-6003","authenticated-orcid":true,"given":"Stefanie","family":"Morosky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 3"},{"name":"Center for Microbial Pathogenesis, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-8002","authenticated-orcid":true,"given":"Dhivyaa","family":"Rajasundaram","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-6309","authenticated-orcid":true,"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical School, Pittsburgh, PA 2"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 3"},{"name":"Center for Microbial Pathogenesis, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,9,25]]},"reference":[{"key":"2023072122144221500_bib1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan2946","article-title":"An immune clock of human pregnancy","volume":"2","author":"Aghaeepour","year":"2017","journal-title":"Sci. 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