{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:12:52Z","timestamp":1787317972473,"version":"build-2736575974"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012021","name":"Iran University of Medical Sciences","doi-asserted-by":"publisher","award":["98-1-4-14329"],"award-info":[{"award-number":["98-1-4-14329"]}],"id":[{"id":"10.13039\/100012021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Leishmania<\/jats:italic>\n                      (L) parasite, the causative agent of zoonotic cutaneous leishmaniasis (ZCL), effectively stimulates the mammalian cells to mount strong humoral responses by enhancing T-helper-2 (Th2)-associated cytokines for its survival. The best strategy to decrease the intensity of infection in the host is induction of cellular immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the effects of the empty bacterial pcDNA3 plasmid on mice infected with\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      and quantified the immune mediators including IFN-\u03b3, IL-4, IL-10, IgG2a, IgG1, arginase activity and nitric oxide (NO) in the mice. Moreover, the footpad lesion size and parasite load were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed that pcDNA3 could modulate the immune responses in favor of host cells and decrease the disease severity. Th2- associated mediators, including arginase, IL-4, and IL-10 are downregulated, while cellular responses are upregulated in line with an increase in the levels of nitric oxide (NO) and interfero-gamma (IFN-\u03b3). Interestingly, pcDNA3 induced specific Th1-associated antibodies, IgG2a isotype; however, it suppressed the production of humoral IgG1. The stimulation of the immune response by the empty pcDNA3 is able to shift the immune function to predominant cellular responses caused by Th1, and it had a positive effect on the treatment of zoonotic cutaneous leishmaniasis (ZCL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Altogether, we introduced the pcDNA3 as a potential interfering factor in the modulation of the immune system against ZCL. Since this vector has been widely used as a control group in different studies, we suggest that the potential function of the empty vector should be deeply assessed, as it exerts anti-parasitic effects on mice infected with\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0263993","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T13:41:26Z","timestamp":1644932486000},"page":"e0263993","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunogenic properties of empty pcDNA3 plasmid against zoonotic cutaneous leishmaniasis in mice"],"prefix":"10.1371","volume":"17","author":[{"given":"Hossein","family":"Montakhab-Yeganeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Shafiei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Najm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Masoori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Aspatwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5315-2559","authenticated-orcid":true,"given":"Alireza","family":"Badirzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"pone.0263993.ref001","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/20477724.2019.1650228","article-title":"Diagnosing Cutaneous leishmaniasis using Fluorescence in Situ Hybridization: the Sri Lankan Perspective.","volume":"113","author":"TD Jayasena Kaluarachchi","year":"2019","journal-title":"Pathogens and Global Health"},{"key":"pone.0263993.ref002","doi-asserted-by":"crossref","first-page":"e0219985","DOI":"10.1371\/journal.pone.0219985","article-title":"Development of an in vitro media perfusion model of Leishmania major macrophage infection","volume":"14","author":"A O\u2019Keeffe","year":"2019","journal-title":"PLOS ONE"},{"key":"pone.0263993.ref003","first-page":"214","article-title":"Clinico-Hematological Findings of Acute Pediatric Visceral Leishmaniasis Referred to the Northeast of Iran during 2005\u20132015","volume":"15","author":"S Barani","year":"2020","journal-title":"Iranian journal of parasitology"},{"key":"pone.0263993.ref004","doi-asserted-by":"crossref","first-page":"107849","DOI":"10.1016\/j.exppara.2020.107849","article-title":"The potential of live attenuated vaccines against Cutaneous Leishmaniasis","volume":"210","author":"A Zabala-Pe\u00f1afiel","year":"2020","journal-title":"Experimental Parasitology"},{"key":"pone.0263993.ref005","doi-asserted-by":"crossref","first-page":"e0007253","DOI":"10.1371\/journal.pntd.0007253","article-title":"Topical paromomycin for New World cutaneous leishmaniasis.","volume":"13","author":"N Sosa","year":"2019","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"pone.0263993.ref006","first-page":"2285","article-title":"Super Infection of Cutaneous Leishmaniasis Caused by Leish-mania major and L. tropica to Crithidia fasciculata in Shiraz","volume":"48","author":"A Mirzapour","year":"2019","journal-title":"Iran. 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