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The presence of SARS\u2010CoV\u20102 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal\u2013fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID\u201019) during their pregnancy. We reported an infiltration of CD163<jats:sup>+<\/jats:sup> macrophages in placenta from COVID\u201019 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature (<jats:italic>NOS<\/jats:italic>2, <jats:italic>IDO1<\/jats:italic>, <jats:italic>IFNG<\/jats:italic>, <jats:italic>TNF<\/jats:italic>, <jats:italic>TGFB<\/jats:italic>) mainly in women infected during the second trimester of pregnancy. COVID\u201019 during pregnancy primed MFM to produce type I and III interferon response to SARS\u2010CoV\u20102 (Wuhan and <jats:italic>\u03b4<\/jats:italic> strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID\u201019 also primed SARS\u2010CoV\u20102 internalization by MFM in an angiotensin\u2010converting enzyme 2\u2010dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS\u2010CoV\u20102 infection, provide a basis for protective placental immunity in COVID\u201019, and highlight the interest of vaccination in pregnant women.<\/jats:p>","DOI":"10.1002\/jmv.29819","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T08:30:39Z","timestamp":1721377839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective role of macrophages from maternal\u2013fetal interface in unvaccinated coronavirus disease 2019 pregnant women"],"prefix":"10.1002","volume":"96","author":[{"given":"Laetitia","family":"Gay","sequence":"first","affiliation":[{"name":"Institut Recherche D\u00e9veloppement, Assistance Publique\u2014H\u00f4pitaux de Marseille, Microbe, Evolution, Phylogeny and Infection Aix\u2010Marseille University  Marseille 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