Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity
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 importan...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-01032-6 |
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| Summary: | 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. |
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| ISSN: | 2059-0105 |