Cargando…

Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis

Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effectiv...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Minmin, Liu, Shutong, Chen, Ying, Liu, Deng, An, Ran, Cai, Haijian, Wang, Jie, Zhou, Nan, Obed, Cudjoe, Han, Meng, Shen, Jilong, Chen, Lijian, Du, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391373/
https://www.ncbi.nlm.nih.gov/pubmed/35986017
http://dx.doi.org/10.1038/s41541-022-00518-5
_version_ 1784770843888320512
author Wu, Minmin
Liu, Shutong
Chen, Ying
Liu, Deng
An, Ran
Cai, Haijian
Wang, Jie
Zhou, Nan
Obed, Cudjoe
Han, Meng
Shen, Jilong
Chen, Lijian
Du, Jian
author_facet Wu, Minmin
Liu, Shutong
Chen, Ying
Liu, Deng
An, Ran
Cai, Haijian
Wang, Jie
Zhou, Nan
Obed, Cudjoe
Han, Meng
Shen, Jilong
Chen, Lijian
Du, Jian
author_sort Wu, Minmin
collection PubMed
description Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4(+) and CD8(+) T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.
format Online
Article
Text
id pubmed-9391373
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-93913732022-08-21 Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis Wu, Minmin Liu, Shutong Chen, Ying Liu, Deng An, Ran Cai, Haijian Wang, Jie Zhou, Nan Obed, Cudjoe Han, Meng Shen, Jilong Chen, Lijian Du, Jian NPJ Vaccines Article Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4(+) and CD8(+) T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis. Nature Publishing Group UK 2022-08-20 /pmc/articles/PMC9391373/ /pubmed/35986017 http://dx.doi.org/10.1038/s41541-022-00518-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Minmin
Liu, Shutong
Chen, Ying
Liu, Deng
An, Ran
Cai, Haijian
Wang, Jie
Zhou, Nan
Obed, Cudjoe
Han, Meng
Shen, Jilong
Chen, Lijian
Du, Jian
Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title_full Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title_fullStr Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title_full_unstemmed Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title_short Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
title_sort live-attenuated me49δcdpk3 strain of toxoplasma gondii protects against acute and chronic toxoplasmosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391373/
https://www.ncbi.nlm.nih.gov/pubmed/35986017
http://dx.doi.org/10.1038/s41541-022-00518-5
work_keys_str_mv AT wuminmin liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT liushutong liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT chenying liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT liudeng liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT anran liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT caihaijian liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT wangjie liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT zhounan liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT obedcudjoe liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT hanmeng liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT shenjilong liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT chenlijian liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis
AT dujian liveattenuatedme49dcdpk3strainoftoxoplasmagondiiprotectsagainstacuteandchronictoxoplasmosis