{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T14:18:46Z","timestamp":1768918726554,"version":"3.49.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Maternal tolerance during pregnancy increases the risk of infection with certain intracellular pathogens. Systemic <jats:italic>Salmonella enterica<\/jats:italic> serovar Typhimurium (<jats:italic>S<\/jats:italic>.Tm) infection during pregnancy in normally resistant 129X1\/SvJ mice leads to severe placental infection, as well as fetal and maternal deaths. However, the effect of oral infection with <jats:italic>S<\/jats:italic>.Tm in pregnant mice and the roles of infection\u2010induced inflammation and cell death pathways in contributing to susceptibility to infection are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Non\u2010pregnant and pregnant C57BL\/6J wild\u2010type (WT) and cell death pathway\u2010altered mice (IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup>, Caspase\u20101, 11<jats:sup>\u2212\/\u2212<\/jats:sup>, RIP3<jats:sup>\u2212\/\u2212<\/jats:sup>) were infected orally with <jats:italic>S<\/jats:italic>.Tm. Host survival and fetal resorption were determined. Bacterial burden in mesenteric lymph nodes (MLNs), spleen, liver, and placentas was enumerated at various time points post\u2010infection. Serum cytokine expression was measured through cytometric bead array.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Oral infection of WT mice with <jats:italic>S<\/jats:italic>.Tm on days 9\u201310 of gestation resulted in systemic dissemination of the bacteria, substantial placental colonization, and fetal loss 5\u00a0days post\u2010infection. Histopathological examination of the placentas indicated that infection\u2010induced widespread focal necrosis and neutrophil infiltration throughout the spongiotrophoblast (SpT) layer. In the non\u2010pregnant state, IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited increased survival following oral <jats:italic>S<\/jats:italic>.Tm infection relative to Caspase\u20101, 11<jats:sup>\u2212\/\u2212<\/jats:sup>, RIP3<jats:sup>\u2212\/\u2212<\/jats:sup>, and WT mice. The increased resistance to <jats:italic>S<\/jats:italic>.Tm infection in IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup> mice was seen during pregnancy as well, with decreased bacterial burden within MLNs, spleen, and placenta, which correlated with the decreased resorptions relative to WT and Caspase\u20101, 11<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Oral <jats:italic>S<\/jats:italic>.Tm exposure leads to placental infection, inflammation, and resorption, whereas IFNAR1 deficiency enhances host resistance both in the non\u2010pregnant and pregnant states.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13454","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T09:18:20Z","timestamp":1621070300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["IFN\u2010alpha receptor deficiency enhances host resistance to oral 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