{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:40:47Z","timestamp":1790613647866,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,18]]},"abstract":"<jats:p>\n                    Recovery from natural or experimental\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    infection, the causative agent of cutaneous leishmaniasis, results in development of durable immunity in mice and humans that is manifested as rapid control of parasite replication and resolution of cutaneous lesion after secondary challenge. This form of \u201cinfection-induced\u201d immunity is thought to occur naturally in endemic areas and is generally considered the gold standard for any effective vaccine against cutaneous leishmaniasis. To determine factors that might heighten or abrogate infection-induced immunity, we investigated the impact of inoculating dead antigen in the form of killed\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites to healed mice. We show that inoculation of killed parasites into mice that resolved their primary virulent\n                    <jats:italic>L. major<\/jats:italic>\n                    infection results in rapid and relatively sustained loss of infection-induced immunity. This loss of immunity was not due to the inability of killed parasites to induce inflammatory responses (such as delayed type hypersensitivity), but it was related to their failure to induce robust IFN-\u03b3 response. Furthermore, inoculation of killed\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites into healed mice led to rapid expansion of IL-10-producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    T cells in lymph nodes draining the primary infection site. Treatment with anti-CD25 or anti-IL-10R mAb abolished killed parasite-induced loss of immunity. Our study suggests that vaccination with killed parasites could predispose naturally immune individuals to become susceptible to new infections and\/or disease reactivation. This may account for the lack of efficacy of such vaccines in field trials in endemic regions. These findings have important implications for vaccine design and vaccination strategies against human cutaneous leishmaniasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0905184106","type":"journal-article","created":{"date-parts":[[2009,8,6]],"date-time":"2009-08-06T21:44:13Z","timestamp":1249595053000},"page":"13951-13956","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Inoculation of killed\n                    <i>Leishmania major<\/i>\n                    into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process"],"prefix":"10.1073","volume":"106","author":[{"given":"Ifeoma","family":"Okwor","sequence":"first","affiliation":[{"name":"Parasite Vaccines Development Laboratory, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0T5 Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Parasite Vaccines Development Laboratory, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0T5 Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Beverley","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude E.","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Parasite Vaccines Development Laboratory, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0T5 Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,8,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.001055"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.2.229-243.2001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7904381"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/4000"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.220-226.1993"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri933"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00844.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830221206"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.9.3730-3738.1993"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01152"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.12.6967"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00626.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/498042"},{"key":"e_1_3_3_14_2","first-page":"159","article-title":"The adjuvant effects of IL-12 and BCG on autoclaved Leishmania major vaccine in experimental cutaneous leishmaniasis","volume":"36","author":"Michel MY","year":"2006","unstructured":"MY Michel, et al., The adjuvant effects of IL-12 and BCG on autoclaved Leishmania major vaccine in experimental cutaneous leishmaniasis. J Egypt Soc Parasitol 36, 159\u2013176, following 76. 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