Protective function of nitric oxide in murine Salmonella infection

Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. Host defense functions of NO are well known for a wide variety of bacterial infections. NO biosynthesis, particularly through expression of inducible NO synthase (iNOS), occurs in a variety microbial infection including Salmonella infection. Excessive NO production for long period allows generation of highly reactive nitrogen species, peroxynitrite (ONOO⁻), via radical coupling reaction of NO and superoxide. It is hypothesized that endogenously produced ONOO⁻ functions as an antimicrobial agent during infection. Intracellular Salmonella species are a significant cause of morbidity and mortality among human populations. iNOS-deficient mice were highly susceptible to Salmonella enterica serovar Typhimurium infection. In addition to direct microbicidal actions, NO or its congeners have immunoregulatory effects relevant to the control of infection. Salmonella infection in iNOS-deficient mice caused higher apoptotic changes leading to extensive liver damage as compared with that of wild-type mice. Here we discussed the host defense function of NO in vivo, in view of its antimicrobial effect against Salmonella and its cytoprotective effect on host cells during Salmonella infection.