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

iScience

Guangdong Provincial Key Laboratory of Aquatic Economic Animals, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, The People's Republic of China.

Published: November 2021

AI Article Synopsis

  • Nitric oxide (NO) is crucial for immune defense against pathogens, but its absence in inducible nitric oxide synthase knockout Sprague Dawley rats shows these rats can resist infection entirely.
  • Infection in rat peritoneal macrophages leads to high reactive oxygen species (ROS) levels due to GRA43, which damages cell membranes and triggers cell death.
  • The study highlights the relationship between NO and ROS in immunity, suggesting that the -SD rat may possess an alternative innate immune system against infections.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571494PMC
http://dx.doi.org/10.1016/j.isci.2021.103280DOI Listing

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