Downregulation of IRF7-mediated Type-I Interferon Response by LmCen Parasites is Necessary for Protective Immunity

Overview

Journal NPJ Vaccines

Date 2024 Dec 20

PMID 39702382

Authors

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

Affiliations

Soon will be listed here.

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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