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In this study, we explored the mechanism of cross-protection against cutaneous lesion-causing Leishmania mexicana. Upon challenge with wild-type L. mexicana, mice immunized either for short or long periods showed significant protection. Immunohistochemical analysis of ears from immunized\/challenged mice exhibited significant influx of macrophages, as well as cells expressing MHC class II and inducible NO synthase, suggesting an induction of potent host-protective proinflammatory responses. In contrast, substantial inhibition of IL-10, IL-4, and IL-13 expression and the absence of degranulated mast cells and less influx of eosinophils within the ears of immunized\/challenged mice suggested a controlled anti-inflammatory response. L. mexicana Ag\u2013stimulated lymph node cell culture from the immunized\/challenged mice revealed induction of IFN-\u03b3 secretion by the CD4 and CD8 T cells compared with non-immunized\/challenged mice. We also observed suppression of Th2 cytokines in the culture supernatants of immunized\/challenged lymph nodes compared with non-immunized\/challenged mice. Adoptively transferred total T cells from immunized mice conferred strong protection in recipient mice against L. mexicana infection, suggesting that attenuated L. donovani can provide protection against heterologous L. mexicana parasites by induction of a strong T cell response. Furthermore, bone marrow\u2013derived dendritic cells infected with LdCen\u2212\/\u2212 and Ldp27\u2212\/\u2212 parasites were capable of inducing a strong proinflammatory response leading to the proliferation of Th1 cells. These studies demonstrate the potential of live-attenuated L. donovani parasites as pan\u2013Leishmania species vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.1303145","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T02:55:32Z","timestamp":1409021732000},"page":"3513-3527","source":"Crossref","is-referenced-by-count":56,"title":["Characterization of Cross-Protection by Genetically Modified Live-Attenuated <i>Leishmania donovani<\/i> Parasites against <i>Leishmania mexicana<\/i>"],"prefix":"10.1093","volume":"193","author":[{"given":"Ranadhir","family":"Dey","sequence":"first","affiliation":[{"name":"Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center , Columbus, OH 42310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parna","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center , Columbus, OH 42310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep K","family":"Dagur","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Terrazas","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center , Columbus, OH 42310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angamuthu","family":"Selvapandiyan","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine , New Delhi 110020 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John P","family":"McCoy","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay R","family":"Satoskar","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University Wexner Medical Center , Columbus, OH 42310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira L","family":"Nakhasi","sequence":"additional","affiliation":[{"name":"Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"2025030707363636600_r1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/00034983.1995.11813017","article-title":"Vaccines against leishmaniasis","volume":"89","author":"Modabber","year":"1995","journal-title":"Ann. 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