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We developed a dermotropic <jats:italic>Leishmania major<\/jats:italic> centrin gene-deleted strain (<jats:italic>LmCen<\/jats:italic><jats:sup>\u2013<jats:italic>\/<\/jats:italic>\u2013<\/jats:sup>) as a live attenuated vaccine. Recent studies have shown that type I interferons (IFNs) play important roles in immunity to parasitic and viral pathogens. However, their relevance in protective immunity following vaccination is not understood. We found that immunization with <jats:italic>LmCen<\/jats:italic><jats:sup><jats:italic>\u2013\/\u2013<\/jats:italic><\/jats:sup> induces a transient increase in type I IFN response along with its regulatory factor IRF7 that is downregulated 7\u201321 days post-immunization, coincided with the induction of a robust Th1 adaptive immune response. Challenge infection with virulent <jats:italic>L. donovani<\/jats:italic> parasites showed a significant reduction of splenic and hepatic parasite burden in IRF7<jats:sup>\u2013\/\u2013<\/jats:sup> mice than wild type mice following immunization with <jats:italic>LmCen<\/jats:italic><jats:sup><jats:italic>\u2013\/\u2013<\/jats:italic><\/jats:sup>, suggesting that ablation of type I IFN response is a pre-requisite for the induction of <jats:italic>LmCen<\/jats:italic><jats:sup><jats:italic>\u2013\/<\/jats:italic>\u2013<\/jats:sup> mediated Th1 immunity against <jats:italic>L. donovani<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/s41541-024-01032-6","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T12:30:32Z","timestamp":1734611432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Downregulation of IRF7-mediated type-I interferon response by LmCen\u2013\/\u2013 parasites is necessary for protective immunity"],"prefix":"10.1038","volume":"9","author":[{"given":"Telly","family":"Sepahpour","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jalal","family":"Alshaweesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazli","family":"Azodi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Komudi","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek D. 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