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 |