Downregulation of IRF7-mediated type-I interferon response by LmCen-/- parasites is necessary for protective immunity.

Leishmaniasis is a tropical disease caused by Leishmania parasites and currently has no licensed vaccines. We developed a dermotropic Leishmania major centrin gene-deleted strain (LmCen^-/-) 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 LmCen^-/- induces a transient increase in type I IFN response along with its regulatory factor IRF7 that is downregulated 7-21 days post-immunization, coincided with the induction of a robust Th1 adaptive immune response. Challenge infection with virulent L. donovani parasites showed a significant reduction of splenic and hepatic parasite burden in IRF7^-/- mice than wild type mice following immunization with LmCen^-/-, suggesting that ablation of type I IFN response is a pre-requisite for the induction of LmCen^-/- mediated Th1 immunity against L. donovani infection.