Allele-Specific Effects of ecSOD in Bacterial Infection

Abstract

Extracellular superoxide dismutase (ecSOD) is the only enzyme that scavenges superoxide specifically in the extracellular compartment. Recent studies indicate that ecSOD is important for protecting tissues from oxidative damage by dampening immune responses but imply that the immunosuppressive effect may be counterproductive during acute infections against invading microorganisms. Although many studies have revealed the importance of the reactive oxygen species (ROS) in bacterial killing, the role of ecSOD during bacterial infection is beginning to be understood. In this study, Listeria monogytogene and Streptococcus pneumoniae were used to infect mice expressing various level of ecSOD: congenic mice sod3129 (relatively high), sod3wt and sod3 KO mice (none). ecSOD expression is inversely related to bacterial clearance. On the other hand, bacterial infection significantly decreases ecSOD activity in infected tissues, while the protein levels are not affected. The induction of iNOS expression is significantly lower in the liver and spleen of sod3 KO mice when compared to those of congenic sod3129 and sod3wt mice. The NO levels in liver and spleen were independent on the level of iNOS induction. However, the NO levels in plasma were significantly induced regardless of the genotype. The oxidative stress levels measured by nitrotyrosine immunoblotting in plasma and liver were significantly higher in sod3 KO mice compared to the congenic sod3129 and sod3wt mice. In conclusion, high ecSOD expression impairs the bacterial clearance and the infection diminishes the ecSOD activity. These data provide a potential target for therapeutic intervention for acute infection.