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.

As a key component of innate immunity, inflammasome is critical for host antitoxoplasmosis immunity, but the underlying mechanisms are still elusive. In this study, we found that inflammasome signaling was activated by PAMPs of T. gondii , which generated a protective immunity against T. gondii invasion by suppressing type I interferon (IFN-I) production. Mechanically, inflammasome-coupled IL-1β signaling triggered the expression of negative regulator SOCS1, which bound to IRF3 to inhibit IFN-I production.

Ti t l eTe m p e r a t u r e is a k ey fac t o r influ e n ci n g t h e inv a sio n a n d p r olife r a tio n of Toxo pl a s m a g o n dii in fis h c ells