Protective Role of Nitric Oxide inStaphylococcus aureusInfection in Mice

Abstract

This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureusinfections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureusinfection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.

The gills are an important site of iNOS expression in rainbow trout Oncorhynchus mykiss after challenge with the Gram‐positive pathogen Renibacterium salmoninarum

“…Sasaki et al . 38 detected expression of iNOS mRNA in spleen and kidney of mice 3 hr after intravenous infection with Staphylococcus aureus . Lamarque et al .…”

Effect of inhibition of inducible nitric oxide synthase (iNOS) on the murine splenic immune response induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans lipopolysaccharide

“…Therefore, the results obtained in the present study are not unexpected. Similarly, the production of NO by Staphylococcus aureus-stimulated murine spleen cells could be inhibited by an iNOS inhibitor, such as aminoguanidine (22). Stenger et al also demonstrated that l-NIL suppressed the production of NO and iNOS activity in Escherichia coli LPS-stimulated murine macrophages (18).…”

Inability to sustain intraphagolysosomal killing ofStaphylococcus aureuspredisposes to bacterial persistence in macrophages

“…The net effect of incomplete killing is accumulation of viable intracellular bacteria. Microbicidal killing involves NADPH oxidase stimulation and activation of proteases (Flannagan et al, 2009), as well as nitric oxide (Sasaki et al, 1998), and these macrophage microbicidal mechanisms are enhanced by IFN-γ (Cassatella et al, 1985;Totemeyer et al, 2006). We addressed whether the killing capacity of macrophages could be enhanced by IFN-γ and whether this would prevent intracellular bacterial persistence.…”