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High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase (iNOS) knockout rats

Wang, Z-J; Yu, S-M; Gao, J-M; Zhang, P; Hide, G; Yamamoto, M; Lai, D-H; Lun, Z-R

Authors

Z-J Wang

S-M Yu

J-M Gao

P Zhang

M Yamamoto

D-H Lai

Z-R Lun



Abstract

Nitric oxide (NO) is an important immune molecule which acts against extra- and intracellular pathogens in most hosts. However, after 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 (PM) 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.

Citation

Wang, Z.-J., Yu, S.-M., Gao, J.-M., Zhang, P., Hide, G., Yamamoto, M., …Lun, Z.-R. (2021). High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase (iNOS) knockout rats. iScience, 24(11), 103280. https://doi.org/10.1016/j.isci.2021.103280

Journal Article Type Article
Acceptance Date Oct 13, 2021
Online Publication Date Oct 15, 2021
Publication Date Nov 19, 2021
Deposit Date Oct 18, 2021
Publicly Available Date Oct 18, 2021
Journal iScience
Print ISSN 2589-0042
Publisher Cell Press
Volume 24
Issue 11
Pages 103280
DOI https://doi.org/10.1016/j.isci.2021.103280
Publisher URL https://doi.org/10.1016/j.isci.2021.103280
Related Public URLs https://www.cell.com/iscience/home
Additional Information Additional Information : ** Article version: AM ** From Elsevier via Jisc Publications Router ** Licence for AM version of this article starting on 14-10-2021: http://creativecommons.org/licenses/by-nc-nd/4.0/ **Journal IDs: issn 25890042 **History: issued 15-10-2021; accepted 13-10-2021
Funders : National Key R&D Program of China;National Natural Science Foundation of China;University of Salford
Grant Number: 2017YFD0500400
Grant Number: 31772445

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