{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:06:26Z","timestamp":1768712786778,"version":"3.49.0"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["PJT-159730"],"award-info":[{"award-number":["PJT-159730"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","award":["PJT-159730"],"award-info":[{"award-number":["PJT-159730"]}]},{"name":"Fonds de recherche du Qu\u00e9bec\u2013Sant\u00e9 (FRQS)","award":["PJT-159730"],"award-info":[{"award-number":["PJT-159730"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The survival, growth, and virulence of Leishmania spp., a group of protozoan parasites, depends on the proper access and regulation of iron. Macrophages, Leishmania\u2019s host cell, may divert iron traffic by reducing uptake or by increasing the efflux of iron via the exporter ferroportin. This parasite has adapted by inhibiting the synthesis and inducing the degradation of ferroportin. To study the role of iron in leishmaniasis, we employed Hjv\u2212\/\u2212 mice, a model of hemochromatosis. The disruption of hemojuvelin (Hjv) abrogates the expression of the iron hormone hepcidin. This allows unrestricted iron entry into the plasma from ferroportin-expressing intestinal epithelial cells and tissue macrophages, resulting in systemic iron overload. Mice were injected with Leishmania major in hind footpads or intraperitoneally. Compared with wild-type controls, Hjv\u2212\/\u2212 mice displayed transient delayed growth of L. major in hind footpads, with a significant difference in parasite burden 4 weeks post-infection. Following acute intraperitoneal exposure to L. major, Hjv\u2212\/\u2212 peritoneal cells manifested increased expression of inflammatory cytokines and chemokines (Il1b, Tnfa, Cxcl2, and Ccl2). In response to infection with L. infantum, the causative agent of visceral leishmaniasis, Hjv\u2212\/\u2212 and control mice developed similar liver and splenic parasite burden despite vastly different tissue iron content and ferroportin expression. Thus, genetic iron overload due to hemojuvelin deficiency appears to mitigate the early development of only cutaneous leishmaniasis.<\/jats:p>","DOI":"10.3390\/ijms24021669","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"1669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic Iron Overload Hampers Development of Cutaneous Leishmaniasis in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-3528","authenticated-orcid":false,"given":"Edouard","family":"Charlebois","sequence":"first","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"},{"name":"Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yupeng","family":"Li","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"},{"name":"Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Wagner","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC J2S 2M2, Canada"},{"name":"Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-0057","authenticated-orcid":false,"given":"Kostas","family":"Pantopoulos","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"},{"name":"Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3901-6638","authenticated-orcid":false,"given":"Martin","family":"Olivier","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1017\/pao.2018.15","article-title":"ROS regulate differentiation of visceralizing Leishmania species into the virulent amastigote form","volume":"4","author":"Khan","year":"2018","journal-title":"Parasitol. 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