Reactive oxygen and nitrogen species and innate immune response

Abstract

The innate immune system is the first line of defense against pathogens and is characterized by its fast but nonspecific response. One important mechanism of this system is the production of the biocidal reactive oxygen and nitrogen species, which are widely distributed within biological systems, including phagocytes and secretions. Reactive oxygen and nitrogen species are short-lived intermediates that are biochemically synthesized by various enzymatic reactions in aerobic organisms and are regulated by antioxidants. The physiological levels of reactive species play important roles in cellular signaling and proliferation. However, higher concentrations and prolonged exposure can fight infections by damaging important microbial biomolecules. One feature of the reactive species generation system is the interaction between its components to produce more biocidal agents. For example, the phagocytic NADPH oxidase complex generates superoxide, which functions as a precursor for antimicrobial hydrogen peroxide synthesis. Peroxide is then used by myeloperoxidase in the same cells to generate hypochlorous acid, a highly microbicidal agent. Studies on animal models and microorganisms have shown that deficiency of these antimicrobial agents is associated with severe recurrent infections and immunocompromised diseases, such as chronic granulomatous disease. There is accumulating evidence that reactive species have important positive aspects on human health and immunity; however, some important promising features of this system remain obscure.