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

IF 6.9 1区医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-12-19 DOI:10.1038/s41541-024-01032-6

Telly Sepahpour, Jalal Alshaweesh, Nazli Azodi, Komudi Singh, Derek D C Ireland, Farzaneh Valanezhad, Risa Nakamura, Abhay R Satoskar, Ranadhir Dey, Shinjiro Hamano, Hira L Nakhasi, Sreenivas Gannavaram

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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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LmCen-/-寄生虫下调irf7介导的i型干扰素反应是保护性免疫所必需的。

利什曼病是一种由利什曼原虫寄生虫引起的热带病，目前尚无获得许可的疫苗。我们开发了一种亲肤性利什曼原虫主要中心蛋白基因缺失菌株（LmCen-/-）作为减毒活疫苗。最近的研究表明，I型干扰素（ifn）在对寄生虫和病毒病原体的免疫中起着重要作用。然而，它们与疫苗接种后保护性免疫的相关性尚不清楚。我们发现，LmCen-/-免疫可诱导I型IFN反应的短暂增加，其调节因子IRF7在免疫后7-21天下调，与诱导强大的Th1适应性免疫反应相一致。在LmCen-/-免疫后，IRF7-/-小鼠的脾脏和肝脏寄生虫负荷比野生型小鼠显著减少，这表明消除I型IFN反应是诱导LmCen-/-介导的Th1免疫对抗多诺多氏杆菌感染的先决条件。

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来源期刊

NPJ Vaccines Immunology and Microbiology-Immunology

CiteScore

11.90

自引率

4.30%

发文量

146

审稿时长

11 weeks

期刊介绍： Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.