High resistance to infection in inducible nitric oxide synthase knockout rats.

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 ( ) in Sprague Dawley (SD) rats, these rats were found to be completely resistant to infection. Once the rat peritoneal macrophages (PMs) were infected with , they produced high levels of reactive oxygen species (ROS) triggered by GRA43 secreted by , 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 infection, in the -SD rat, demonstrates a strong link between NO and ROS in immunity to infection and showcases a potentially novel and effective backup innate immunity system.