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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Autores principales: Zhen-Jie Wang, Shao-Meng Yu, Jiang-Mei Gao, Peng Zhang, Geoff Hide, Masahiro Yamamoto, De-Hua Lai, Zhao-Rong Lun
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/8c9f5c074b0648d6a4527f5d3c947cc1
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Immunology
Microbiology
Parasitology
Science
Q
spellingShingle 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
description 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
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