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Immunol."],"abstract":"<jats:p>Males are generally more susceptible to <jats:italic>Nocardia<\/jats:italic> infection than females, with a male-to-female ratio of 2 and higher clinical disease. 17\u03b2-Estradiol has been implicated in affecting the sex-based gap by inhibiting the growth of <jats:italic>N. brasiliensis<\/jats:italic> in experiments, but the underlying mechanisms have not yet been fully clarified. In the present study, however, we report increased severity in <jats:italic>N. farcinica<\/jats:italic> IFM 10152-infected female mice compared with male mice with increased mortality, elevated lung bacterial loads and an exaggerated pulmonary inflammatory response, which was mimicked in ovariectomized female mice supplemented with E2. Similarly, the overwhelming increase in bacterial loads was also evident in E2-treated host cells, which were associated with downregulating the phosphorylation level of the MAPK pathway by binding the estrogen receptor. We conclude that although there are more clinical cases of <jats:italic>Nocardia<\/jats:italic> infection in males, estrogen promotes the survival of the bacteria, which leads to aggravated inflammation in females. Our data emphasize the need to include and separately analyze both sexes in future studies of <jats:italic>Nocardia<\/jats:italic> to understand the sex differences in immune responses and disease pathogenesis.<\/jats:p>","DOI":"10.3389\/fimmu.2022.858609","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T04:54:44Z","timestamp":1646196884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Estradiol Aggravate Nocardia farcinica Infections in Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Lichao","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhao","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.19.2.259-282.2006","article-title":"Clinical and Laboratory Features of the Nocardia Spp. Based on Current Molecular Taxonomy","volume":"19","author":"Brown-Elliott","year":"2006","journal-title":"Clin Microbiol Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2011.11.016","article-title":"Nocardiosis: Updates and Clinical Overview","volume":"87","author":"Wilson","year":"2012","journal-title":"Mayo Clin Proc"},{"key":"B3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s15010-009-9193-9","article-title":"Nocardiosis: Updated Clinical Review and Experience at a Tertiary Center","volume":"38","author":"Ambrosioni","year":"2010","journal-title":"Infection"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.590239","article-title":"Isolated Nocardiosis, an Unrecognized Primary Immunodeficiency","volume":"11","author":"Mart\u00ednez-Barricarte","year":"2020","journal-title":"Front Immunol"},{"key":"B5","article-title":"Actualizaci\u00f3n De La Epidemiolog\u00eda Del Micetoma En M\u00e9xico. 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