Extracellular superoxide dismutase impairs neutrophil function and clearance of Listeria monocytogenes (118.4)

Abstract

Abstract It is well established that reactive oxygen species (ROS) play a critical role during immune responses against pathogens. Extracellular superoxide dismutase (ecSOD) regulates extracellular concentrations of ROS and protects tissues during non-infectious inflammatory insults. However, how ecSOD activity impacts immune responses directed against pathogenic microorganisms has not been thoroughly investigated. We utilized mice with varying levels of ecSOD activity to investigate the involvement of this enzyme in innate immune responses against Listeria monocytogenes. Our data demonstrate that ecSOD activity negatively impacted host survival and bacterial clearance from the spleen and liver. Paradoxically, ecSOD activity was associated with increased percentages of neutrophils in the livers of mice prior to, and during infection. Neutrophils from livers of mice with high ecSOD activity were altered in their ability to produce various molecules important for bacterial clearance. Additionally, ecSOD activity was associated with a higher percentage of neutrophils that phenotypically resembled myeloid-derived suppressor cells. Neutrophil depletion studies revealed that high ecSOD activity resulted in neutrophils with no protective capacity, whereas neutrophils from mice lacking ecSOD provided superior protection compared to neutrophils from wild-type mice. Collectively, our data demonstrate that ecSOD activity inhibits innate immune responses, thus impairing bacterial clearance.