{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:13:36Z","timestamp":1761488016888,"version":"3.37.3"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2008,3,17]],"date-time":"2008-03-17T00:00:00Z","timestamp":1205712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007637","name":"National Program of Science and Technology in Health","doi-asserted-by":"publisher","award":["22290414328","22290412603"],"award-info":[{"award-number":["22290414328","22290412603"]}],"id":[{"id":"10.13039\/100007637","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Projects","award":["AI 061624"],"award-info":[{"award-number":["AI 061624"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Laval, Canada"},{"name":"CIDEIM"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The maintenance of host defense during pregnancy may depend on heightened innate immunity. We evaluated the immune response of pregnant hamsters during early infection with Leishmania (Viannia) panamensis, a cause of American cutaneous leishmaniasis. At 7 days post-infection, pregnant animals showed a lower parasite burden compared with nonpregnant controls at the cutaneous infection site (P=0.0098) and draining lymph node (P=0.02). Resident peritoneal macrophages and neutrophils from pregnant animals had enhanced Leishmania killing capacity compared with nonpregnant controls (P=0.018 each). This enhanced resistance during pregnancy was associated with increased expression of inducible NO synthase (iNOS) mRNA in lymph node cells (P=0.02) and higher NO production by neutrophils (P=0.0001). Macrophages from nonpregnant hamsters infected with L. panamensis released high amounts of NO upon estrogen exposure (P=0.05), and addition of the iNOS inhibitor L-N6-(1-iminoethyl) lysine blocked the induction of NO production (P=0.02). Infected, nonpregnant females treated with estrogen showed a higher percentage of cells producing NO at the infection site than controls (P=0.001), which correlated with lower parasite burdens (P=0.036). Cultured macrophages or neutrophils from estrogen-treated hamsters showed significantly increased NO production and Leishmania killing compared with untreated controls. iNOS was identified as the likely source of estrogen-induced NO in primed and na\u00efve macrophages, as increased transcription was evident by real-time PCR. Thus, the innate defense against Leishmania infection is heightened during pregnancy, at least in part as a result of estrogen-mediated up-regulation of iNOS expression and NO production.<\/jats:p>","DOI":"10.1189\/jlb.0207130","type":"journal-article","created":{"date-parts":[[2008,3,18]],"date-time":"2008-03-18T00:49:22Z","timestamp":1205801362000},"page":"1413-1422","source":"Crossref","is-referenced-by-count":30,"title":["Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production"],"prefix":"10.1093","volume":"83","author":[{"given":"Yaneth","family":"Osorio","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Texas, Health Science Center , San Antonio, Texas , USA"},{"name":"Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM , Cali, Colombia"},{"name":"Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System , San Antonio, Texas , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana L","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM , Cali, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex G","family":"Peniche","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM , Cali, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C","family":"Melby","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Texas, Health Science Center , San Antonio, Texas , USA"},{"name":"Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System , San Antonio, Texas , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno L","family":"Travi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Texas, Health Science Center , San Antonio, Texas , USA"},{"name":"Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM , Cali, Colombia"},{"name":"Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System , San Antonio, Texas , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,3,17]]},"reference":[{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s000110050332","article-title":"Estrogen-mediated immunosuppression in autoimmune diseases","volume":"47","author":"Jansson","year":"1998","journal-title":"Inflamm. 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Soc."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0022-3956(96)00055-6","article-title":"Gender differences in host defense mechanisms","volume":"31","author":"Cannon","year":"1997","journal-title":"J. Psychiatr. Res."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1749-6632.1988.tb27216.x","article-title":"Somatotropin and prolactin enhance respiratory burst activity of macrophages","volume":"540","author":"Edwards","year":"1988","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1084\/jem.183.4.1501","article-title":"Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase","volume":"183","author":"Stenger","year":"1996","journal-title":"J. Exp. 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Parasitol."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1440-1711.1998.00730.x","article-title":"Sex-determined resistance against Leishmania mexicana is associated with the preferential induction of a Th1-like response and IFN-\u03b3 production by female but not male DBA\/2 mice","volume":"76","author":"Satoskar","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1128\/IAI.70.5.2288-2296.2002","article-title":"Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp","volume":"70","author":"Travi","year":"2002","journal-title":"Infect. 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Parasitol."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"393","DOI":"10.7705\/biomedica.v24i4.1289","article-title":"[Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application]","volume":"24","author":"Henao","year":"2004","journal-title":"Biomedica"},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1128\/IAI.66.5.2135-2142.1998","article-title":"Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of cytokine mRNA expression in experimental visceral leishmaniasis","volume":"66","author":"Melby","year":"1998","journal-title":"Infect. 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Immun."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1128\/iai.58.6.1685-1690.1990","article-title":"Immune T cells sorted by flow cytometry confer protection against infection with Treponema pallidum subsp. pertenue in hamsters","volume":"58","author":"Liu","year":"1990","journal-title":"Infect. Immun."},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1399-0039.1974.tb00252.x","article-title":"Separation of blood leucocytes, granulocytes and lymphocytes","volume":"4","author":"Boyum","year":"1974","journal-title":"Tissue Antigens"},{"key":"2023033005124610900_","doi-asserted-by":"crossref","first-page":"R1902","DOI":"10.1152\/ajpregu.2001.280.6.R1902","article-title":"Effect of 5 \u03b1-pregnan-3 \u03b1-ol-20-one on nitric oxide biosynthesis and plasma volume in rats","volume":"280","author":"Lo","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Comp. 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