RRC ID 82600
Author Sepahpour T, Alshaweesh J, Azodi N, Singh K, Ireland DDC, Valanezhad F, Nakamura R, Satoskar AR, Dey R, Hamano S, Nakhasi HL, Gannavaram S.
Title Downregulation of IRF7-mediated type-I interferon response by LmCen-/- parasites is necessary for protective immunity.
Journal NPJ Vaccines
Abstract 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.
Volume 9(1)
Pages 250
Published 2024-12-19
DOI 10.1038/s41541-024-01032-6
PII 10.1038/s41541-024-01032-6
PMID 39702382
PMC PMC11659581
Resource
Mice RBRC01420