SodA promotes immune evasion ofby suppressing ROS accumulation and GSDMD-mediated mitochondrial disruption in neutrophils.

Abstract

UNLABELLED: is a major swine pathogen that poses a serious threat to pig health. Resistance to oxidative stress and modulation of host immune responses are both critical for the survival ofserotype 2 (SS2) strains during infection. In this study, we investigated the role of thegene in SS2 survival, neutrophil responses, and mitochondrial function, focusing particularly on neutrophil extracellular trap (NET) formation. Using a murine peritoneal infection model, we found thatdeletion significantly reduced neutrophil recruitment.assays with primary mouse neutrophils further demonstrated that themutant exhibited reduced intracellular survival and elevated levels of reactive oxygen species (ROS) in neutrophils. The mutant also triggered more robust NET formation, as indicated by significantly increased levels of cell-free DNA and MPO-DNA complexes. Importantly, the inclusion of a complemented strain confirmed restoration of ROS clearance and normalization of NETs-associated markers, supporting the specificity of the-dependent phenotype. Moreover,deficiency exacerbated SS2-induced mitochondrial membrane depolarization and ROS accumulation in neutrophils. Notably, it also enhanced the expression of cleaved gasdermin D (GSDMD-N), which colocalized with mitochondria and likely contributed to mitochondrial damage and NET induction. Collectively, these findings suggest thatfacilitates SS2 immune evasion by suppressing host ROS accumulation and GSDMD-N-mediated mitochondrial disruption, thereby limiting NET formation and promoting bacterial survival. IMPORTANCE: is a major swine pathogen with significant economic and zoonotic implications. Neutrophil extracellular traps (NETs) are essential for host defense, but their regulation by bacterial factors remains poorly understood. This study identifies the superoxide dismutase geneas a key factor in immune evasion by. We demonstrate thatdeletion enhances reactive oxygen species accumulation, mitochondrial damage, and NETs formation in neutrophils, impairing bacterial survival. These findings reveal a novel mechanism by whichmodulates host innate immunity and highlightas a potential target for enhancing host defense againstserotype 2 infection.