摘要:SummaryNitric 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, theseiNOS−/−rats were found to be completely resistant toToxoplasma gondiiinfection. Once theiNOS−/−rat peritoneal macrophages (PMs) were infected withT. gondii, they produced high levels of reactive oxygen species (ROS) triggered by GRA43 secreted byT. 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 toT. gondiiinfection, in theiNOS−/−-SD rat, demonstrates a strong link between NO and ROS in immunity toT. gondiiinfection and showcases a potentially novel and effective backup innate immunity system.Graphical abstractDisplay OmittedHighlights•iNOS−/−-SD rats show strong resistance toToxoplasma gondiiinfection•iNOS−/−-SD rat PMs resistT. gondiiinfection through ROS upregulation•TheT. gondiiinfection results in PM pyroptosis iniNOS−/−-SD rats•GRAs play a key role in the activation of resistance iniNOS−/−-SD rat PMsImmunology; Microbiology; Parasitology