{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:38:17Z","timestamp":1790750297849,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ability to manipulate the Leishmania genome to create genetically modified parasites by introducing or eliminating genes is considered a powerful alternative for developing a new generation vaccine against leishmaniasis. Previously, we showed that the deletion of one allele of the Leishmania infantum silent information regulatory 2 (LiSIR2) locus was sufficient to dramatically affect amastigote axenic proliferation. Furthermore, LiSIR2 single knockout (LiSIR2+\/\u2212) amastigotes were unable to replicate in vitro inside macrophages. Because this L. infantum mutant persisted in BALB\/c mice for up to 6 wk but failed to establish an infection, we tested its ability to provide protection toward a virulent L. infantum challenge. Strikingly, vaccination with a single i.p. injection of LiSIR2+\/\u2212 single knockout elicits complete protection. Thus, vaccinated BALB\/c mice showed a reversal of T cell anergy with specific anti-Leishmania cytotoxic activity and high levels of NO production. Moreover, vaccinated mice simultaneously generated specific anti-Leishmania IgG Ab subclasses suggestive of both type 1 and type 2 responses. A strong correlation was found between the elimination of the parasites and an increased Leishmania-specific IFN-\u03b3\/IL-10 ratio. Therefore, we propose that the polarization to a high IFN-\u03b3\/low IL-10 ratio after challenge is a clear indicator of vaccine success. Furthermore these mutants, which presented attenuated virulence, represent a good model to understand the correlatives of protection in visceral leishmaniasis.<\/jats:p>","DOI":"10.4049\/jimmunol.179.5.3161","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:46Z","timestamp":1397848666000},"page":"3161-3170","source":"Crossref","is-referenced-by-count":88,"title":["SIR2-Deficient\n                    <i>Leishmania infantum<\/i>\n                    Induces a Defined IFN-\u03b3\/IL-10 Pattern That Correlates with Protection"],"prefix":"10.1093","volume":"179","author":[{"given":"Ricardo","family":"Silvestre","sequence":"first","affiliation":[{"name":"Departamento de Bioqui\u0301mica da Faculdade de Farma\u0301cia da Universidade do Porto ,","place":["Portugal"]},{"name":"Instituto de Biologia Molecular e Celular da Universidade do Porto ,","place":["Portugal"]},{"name":"Institut de Recherche pour le De\u0301veloppement (IRD), Centre IRD de Montpellier , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabela","family":"Cordeiro-Da-Silva","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica da Faculdade de Farma\u0301cia da Universidade do Porto ,","place":["Portugal"]},{"name":"Instituto de Biologia Molecular e Celular da Universidade do Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Santare\u0301m","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica da Faculdade de Farma\u0301cia da Universidade do Porto ,","place":["Portugal"]},{"name":"Instituto de Biologia Molecular e Celular da Universidade do Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Vergnes","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le De\u0301veloppement (IRD), Centre IRD de Montpellier , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Sereno","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le De\u0301veloppement (IRD), Centre IRD de Montpellier , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ouaissi","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular da Universidade do Porto ,","place":["Portugal"]},{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) , Montpellier ,","place":["France"]},{"name":"Institut de Recherche pour le De\u0301veloppement (IRD), Centre IRD de Montpellier , Montpellier ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2026012809342113800_R1","first-page":"1003","volume-title":"J. 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