High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats
Summary: Nitric oxide (NO) is an important immune molecule that acts against extracellular and intracellular pathogens in most hosts. However, after the knockout of inducible nitric oxide synthase (iNOS−/−) in Sprague Dawley (SD) rats, these iNOS−/− rats were found to be completely resistant to Toxo...
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Elsevier
2021
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oai:doaj.org-article:8c9f5c074b0648d6a4527f5d3c947cc12021-11-20T05:09:16ZHigh resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats2589-004210.1016/j.isci.2021.103280https://doaj.org/article/8c9f5c074b0648d6a4527f5d3c947cc12021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012499https://doaj.org/toc/2589-0042Summary: Nitric oxide (NO) is an important immune molecule that acts against extracellular and intracellular pathogens in most hosts. However, after the knockout of inducible nitric oxide synthase (iNOS−/−) in Sprague Dawley (SD) rats, these iNOS−/− rats were found to be completely resistant to Toxoplasma gondii infection. Once the iNOS−/− rat peritoneal macrophages (PMs) were infected with T. gondii, they produced high levels of reactive oxygen species (ROS) triggered by GRA43 secreted by T. gondii, which damaged the parasitophorous vacuole membrane and PM mitochondrial membranes within a few hours post-infection. Further evidence indicated that the high levels of ROS caused mitochondrial superoxide dismutase 2 depletion and induced PM pyroptosis and cell death. This discovery of complete resistance to T. gondii infection, in the iNOS−/−-SD rat, demonstrates a strong link between NO and ROS in immunity to T. gondii infection and showcases a potentially novel and effective backup innate immunity system.Zhen-Jie WangShao-Meng YuJiang-Mei GaoPeng ZhangGeoff HideMasahiro YamamotoDe-Hua LaiZhao-Rong LunElsevierarticleImmunologyMicrobiologyParasitologyScienceQENiScience, Vol 24, Iss 11, Pp 103280- (2021) |
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Immunology Microbiology Parasitology Science Q Zhen-Jie Wang Shao-Meng Yu Jiang-Mei Gao Peng Zhang Geoff Hide Masahiro Yamamoto De-Hua Lai Zhao-Rong Lun High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
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Summary: Nitric oxide (NO) is an important immune molecule that acts against extracellular and intracellular pathogens in most hosts. However, after the knockout of inducible nitric oxide synthase (iNOS−/−) in Sprague Dawley (SD) rats, these iNOS−/− rats were found to be completely resistant to Toxoplasma gondii infection. Once the iNOS−/− rat peritoneal macrophages (PMs) were infected with T. gondii, they produced high levels of reactive oxygen species (ROS) triggered by GRA43 secreted by T. gondii, which damaged the parasitophorous vacuole membrane and PM mitochondrial membranes within a few hours post-infection. Further evidence indicated that the high levels of ROS caused mitochondrial superoxide dismutase 2 depletion and induced PM pyroptosis and cell death. This discovery of complete resistance to T. gondii infection, in the iNOS−/−-SD rat, demonstrates a strong link between NO and ROS in immunity to T. gondii infection and showcases a potentially novel and effective backup innate immunity system. |
format |
article |
author |
Zhen-Jie Wang Shao-Meng Yu Jiang-Mei Gao Peng Zhang Geoff Hide Masahiro Yamamoto De-Hua Lai Zhao-Rong Lun |
author_facet |
Zhen-Jie Wang Shao-Meng Yu Jiang-Mei Gao Peng Zhang Geoff Hide Masahiro Yamamoto De-Hua Lai Zhao-Rong Lun |
author_sort |
Zhen-Jie Wang |
title |
High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
title_short |
High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
title_full |
High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
title_fullStr |
High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
title_full_unstemmed |
High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
title_sort |
high resistance to toxoplasma gondii infection in inducible nitric oxide synthase knockout rats |
publisher |
Elsevier |
publishDate |
2021 |
url |
https://doaj.org/article/8c9f5c074b0648d6a4527f5d3c947cc1 |
work_keys_str_mv |
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