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To determine the mechanisms involved, we addressed the role of inflammation and bacterial burden in causing placental and systemic disease.<jats:italic>In vitro<\/jats:italic>, choriocarcinoma cells were a highly conducive niche for intracellular<jats:italic>S.<\/jats:italic>Typhimurium proliferation. While infection of mice with<jats:italic>S.<\/jats:italic>Typhimurium wild-type (WT) and mutant (\u0394<jats:italic>aroA<\/jats:italic>and \u0394<jats:italic>invA<\/jats:italic>) strains led to profound pathogen proliferation and massive burden within placental cells, only the virulent WT<jats:italic>S.<\/jats:italic>Typhimurium infection evoked total fetal loss and adverse host outcome. This correlated with substantial placental expression of granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-\u03b1) and increased serum inflammatory cytokines\/chemokines, such as G-CSF, IL-6, CCL1, and KC, evoked by WT<jats:italic>S.<\/jats:italic>Typhimurium infection. In contrast, infection with high doses of<jats:italic>S.<\/jats:italic>Typhimurium \u0394<jats:italic>aroA<\/jats:italic>, despite causing massive placental infection, resulted in reduced inflammatory cellular and cytokine response. While<jats:italic>S.<\/jats:italic>Typhimurium WT bacteria were dispersed in large numbers across all regions of the placenta, including the deeper labyrinth trophoblast,<jats:italic>S.<\/jats:italic>Typhimurium \u0394<jats:italic>aroA<\/jats:italic>bacteria localized primarily to the decidua. This correlated with the widespread placental necrosis accompanied by neutrophil infiltration evoked by the<jats:italic>S.<\/jats:italic>Typhimurium WT bacteria. Thus, the ability of<jats:italic>Salmonella<\/jats:italic>to localize to deeper layers of the placenta and the nature of inflammation triggered by the pathogen, rather than bacterial burden, profoundly influenced placental integrity and host survival.<\/jats:p>","DOI":"10.1128\/iai.01186-09","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T04:34:14Z","timestamp":1267504454000},"page":"2292-2301","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["<i>Salmonella enterica<\/i>Serovar Typhimurium-Induced Placental Inflammation and Not Bacterial Burden Correlates with Pathology and Fatal Maternal Disease"],"prefix":"10.1128","volume":"78","author":[{"given":"Anindita","family":"Chattopadhyay","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, University of Ottawa"},{"name":"Institute for Biological Sciences, National Research Council, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmal","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, University of Ottawa"},{"name":"Institute for Biological Sciences, National Research Council, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep K.","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, University of Ottawa"},{"name":"Institute for Biological Sciences, National Research Council, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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