{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:52:07Z","timestamp":1783392727457,"version":"3.54.6"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI114655"],"award-info":[{"award-number":["AI114655"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI049820"],"award-info":[{"award-number":["AI049820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["PATH"],"award-info":[{"award-number":["PATH"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD075665"],"award-info":[{"award-number":["HD075665"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,3,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    infection. We show that placental syncytiotrophoblasts, multinucleated cells that are in direct contact with maternal blood, restrict\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    infection at two distinct stages of the parasite lytic cycle\u2014at the time of attachment and also during intracellular replication. Utilizing comparative transcriptome sequencing (RNA-seq) transcriptional profiling, we also show that human placental trophoblasts from both the second and third trimesters respond uniquely to\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    infection compared to trophoblast cell lines, typified by the upregulation of several immunity-related genes. One of the most differentially induced genes was the chemokine CCL22, which relies on the secretion of a parasite effector(s) either during or after invasion for its induction. Collectively, our findings provide new insights into the mechanisms by which the human placenta restricts the vertical transmission of\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    at early and late stages of human pregnancy and demonstrate the existence of at least two interferon-independent pathways that restrict\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    access to the fetal compartment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is a major source of congenital disease worldwide and must breach the placental barrier to be transmitted from maternal blood to the developing fetus. The events associated with the vertical transmission of\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    are largely unknown. Here, we show that primary human syncytiotrophoblasts, the fetus-derived cells that comprise the primary placental barrier, restrict\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    infection at two distinct stages of the parasite life cycle and respond to infection by inducing a unique immunomodulatory transcriptional profile. Collectively, our findings provide important insights into the mechanisms by which human syncytiotrophoblasts restrict\n                    <jats:italic>T.\u00a0gondii<\/jats:italic>\n                    infection at early and late stages of human pregnancy, identify both permissive and resistant human placental cell types, and identify the placenta-enriched signaling pathways induced in response to infection.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01678-17","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T05:36:47Z","timestamp":1515389807000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Human Placental Syncytiotrophoblasts Restrict\n                    <i>Toxoplasma gondii<\/i>\n                    Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5527-723X","authenticated-orcid":false,"given":"Stephanie E.","family":"Ander","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"Center for Microbial Pathogenesis, Children\u2019s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth N.","family":"Rudzki","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"Center for Microbial Pathogenesis, 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