EXTRACELLULAR SUPEROXIDE DISMUTASE MODULATES THE ADAPTIVE IMMUNE RESPONSE DURING SECONDARY INTRACELLULAR BACTERIAL INFECTION

Purpose: Listeria monocytogenes (LM) is an intracellular foodborne pathogen that causes severe disease in immunocompromised individuals, spontaneous abortion in pregnant women, and results in ~25% mortality rate in infected individuals, making it one of the leading causes of death from foodborne infection. Extracellular superoxide dismutase (ecSOD) converts superoxide into hydrogen peroxide in the extracellular milieu and protects against oxidative stress. While it has been shown that ecSOD decreases innate immune responses during LM infection, its role in a secondary infection model has not been explored. Methods: Congenic mice with high ecSOD activity (ecSOD HI), wild type ecSOD activity (ecSOD WT), or lacking ecSOD (ecSOD KO), on the C57Bl/6 background, were infected with LM/OVA ΔActA and after 40 days challenged with LM/OVA. Colony forming units (CFUs) were counted to determine bacterial burden in the spleen and liver. Percentages of different cell types were determined by flow cytometry. IFN-𝛾 production and concentrations were determined by flow cytometry and ELISA respectively. Results: Our results indicate that ecSOD is protective in a secondary infection since ecSOD HI mice are better able to control bacterial burden than ecSOD KO mice with the ecSOD WT mice showing intermediate CFUs. The ecSOD KO mice exhibit a significantly lower percentage of dendritic cells and corresponding decreases in percentages of both overall CD8 T cells as well as memory CD8 T cells. There was also a decrease in percentages of overall CD4 T cells and memory CD4 T cells, primarily in the spleen. Additionally, there was a significant decrease in CD8 T cell specific IFN-𝛾 production in the spleen after overnight culture with both specific and non-specific stimulation. Conclusions: Our data indicate that ecSOD plays an important role in modulating cell-mediated adaptive immune responses during secondary intracellular bacterial infection. The combination of decreased dendritic cell and CD8 T cell populations, as well as decreased ability of CD8 T cells to produce IFN-𝛾, in ecSOD KO mice suggest that ecSOD may play a role in facilitating the activation of CD8 T cells and their ability to effectively respond during secondary LM infection.