{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:57:51Z","timestamp":1771005471767,"version":"3.50.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI139576"],"award-info":[{"award-number":["R21AI139576"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD106247"],"award-info":[{"award-number":["R01HD106247"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","award":["PDSE"],"award-info":[{"award-number":["PDSE"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanisms and challenges in replicating trophoblast-pathogen interactions using\n              <jats:italic>in vitro<\/jats:italic>\n              models, we tested an existing stem-cell-derived model of trophoblast development for its relevance to infection with\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              . We grew human trophoblast stem cells (TS\n              <jats:sup>CT<\/jats:sup>\n              ) under conditions leading to either syncytiotrophoblast (TS\n              <jats:sup>SYN<\/jats:sup>\n              ) or cytotrophoblast (TS\n              <jats:sup>CYT<\/jats:sup>\n              ) and infected them with\n              <jats:italic>T. gondii<\/jats:italic>\n              . We evaluated\n              <jats:italic>T. gondii<\/jats:italic>\n              proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TS\n              <jats:sup>SYNs<\/jats:sup>\n              cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by transmission electron microscopy and scanning electron microscopy (SEM), a resistance to\n              <jats:italic>T. gondii<\/jats:italic>\n              adhesion could be visualized on the SEM level. Furthermore, TS\n              <jats:sup>SYNs<\/jats:sup>\n              were highly refractory to parasite adhesion and replication, while TS\n              <jats:sup>CYTs<\/jats:sup>\n              were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to\n              <jats:italic>T. gondii<\/jats:italic>\n              infection. We also evaluated if TS\n              <jats:sup>SC<\/jats:sup>\n              -derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen,\n              <jats:italic>Listeria monocytogenes<\/jats:italic>\n              . We demonstrate that TS\n              <jats:sup>SYNs<\/jats:sup>\n              are highly resistant to\n              <jats:italic>L. monocytogenes<\/jats:italic>\n              , while TS\n              <jats:sup>CYTs<\/jats:sup>\n              are not. Like\n              <jats:italic>T. gondii<\/jats:italic>\n              , TS\n              <jats:sup>SYN<\/jats:sup>\n              resistance to\n              <jats:italic>L. monocytogenes<\/jats:italic>\n              was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell-derived trophoblasts recapitulate resistance profiles of primary cells to\n              <jats:italic>T. gondii<\/jats:italic>\n              and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Congenital toxoplasmosis can cause a devastating consequence to the fetus. To reach the fetus\u2019s tissues,\n                <jats:italic>Toxoplasma gondii<\/jats:italic>\n                must cross the placenta barrier. However, how this parasite crosses the placenta and the precise molecular mechanisms of placental resistance to this parasite are still unknown. In this study, we aimed to characterize a new cellular model of human trophoblast stem cells to determine their resistance, susceptibility, and response to\n                <jats:italic>T. gondii<\/jats:italic>\n                . Syncytiotrophoblast derived from trophoblast stem cells recapitulate the resistance profile similarly to placenta cells. We also showed that these cells are highly resistant to\n                <jats:italic>Listeria monocytogenes<\/jats:italic>\n                , at the level of bacterial adhesion. Our results suggest that resisting pathogen adhesion\/attachment may be a generalized mechanism of syncytiotrophoblast resistance, and trophoblast stem cells represent a promising model to investigate cell-intrinsic mechanisms of resistance to pathogen adhesion and replication.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00748-23","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:06:42Z","timestamp":1716296802000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["The trophoblast surface becomes refractory to adhesion by congenitally transmitted\n            <i>Toxoplasma gondii<\/i>\n            and\n            <i>Listeria monocytogenes<\/i>\n            during cytotrophoblast to syncytiotrophoblast development"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6772-4658","authenticated-orcid":true,"given":"Rafaela J.","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah F.","family":"Cabo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jada L.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2061-319X","authenticated-orcid":true,"given":"Laty A.","family":"Cahoon","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-6309","authenticated-orcid":true,"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0000-9243","authenticated-orcid":true,"given":"Jon P.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Biological 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