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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-01032-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850244223582863360 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Telly Sepahpour |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-71c29b8aa02f42a796fb7a06d64b2816 |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-71c29b8aa02f42a796fb7a06d64b28162025-08-20T01:59:48ZengNature Portfolionpj Vaccines2059-01052024-12-019111210.1038/s41541-024-01032-6Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunityTelly Sepahpour0Jalal Alshaweesh1Nazli Azodi2Komudi Singh3Derek D. C. Ireland4Farzaneh Valanezhad5Risa Nakamura6Abhay R. Satoskar7Ranadhir Dey8Shinjiro Hamano9Hira L. Nakhasi10Sreenivas Gannavaram11Division of Emerging and Transfusion Transmitted Diseases, CBER, FDADepartment of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan, and Graduate School of Biomedical Sciences, Doctoral Leadership Program, Nagasaki UniversityDivision of Emerging and Transfusion Transmitted Diseases, CBER, FDANational Heart Lung Blood Institute (NHLBI), NIHOffice of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug AdministrationDepartment of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan, and Graduate School of Biomedical Sciences, Doctoral Leadership Program, Nagasaki UniversityDepartment of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan, and Graduate School of Biomedical Sciences, Doctoral Leadership Program, Nagasaki UniversityDepartment of Pathology and Microbiology, Ohio State UniversityDivision of Emerging and Transfusion Transmitted Diseases, CBER, FDADepartment of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan, and Graduate School of Biomedical Sciences, Doctoral Leadership Program, Nagasaki UniversityDivision of Emerging and Transfusion Transmitted Diseases, CBER, FDADivision of Emerging and Transfusion Transmitted Diseases, CBER, FDAAbstract 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.https://doi.org/10.1038/s41541-024-01032-6 |
| spellingShingle | 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 Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity npj Vaccines |
| title | Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity |
| title_full | Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity |
| title_fullStr | Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity |
| title_full_unstemmed | Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity |
| title_short | Downregulation of IRF7-mediated type-I interferon response by LmCen –/– parasites is necessary for protective immunity |
| title_sort | downregulation of irf7 mediated type i interferon response by lmcen parasites is necessary for protective immunity |
| url | https://doi.org/10.1038/s41541-024-01032-6 |
| work_keys_str_mv | AT tellysepahpour downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT jalalalshaweesh downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT nazliazodi downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT komudisingh downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT derekdcireland downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT farzanehvalanezhad downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT risanakamura downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT abhayrsatoskar downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT ranadhirdey downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT shinjirohamano downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT hiralnakhasi downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity AT sreenivasgannavaram downregulationofirf7mediatedtypeiinterferonresponsebylmcenparasitesisnecessaryforprotectiveimmunity |