Selenium Supplementation Attenuates NET DNA-Mediated Intestinal Epithelial Pyroptosis and Intestinal Barrier Injury in MRSA Enteritis via Upregulating Selenoprotein S

Abstract It is widely believed that neutrophils exert an antibacterial defense through NETs during MRSA infection. However, this study found that during MRSA enteritis, NET DNA released by neutrophils under low-selenium (Se) conditions directly triggers intestinal epithelial pyroptosis and disrupts tight junctions. Following sodium selenite intervention, intestinal selenoprotein transcriptome screening identified selenoprotein S (SelS) as the most significantly downregulated selenoprotein after the MRSA challenge and the most sensitive to Se supplementation recovery. Notably, MRSA alone did not directly induce pyroptosis or tight junction disruption in MODE-K cells, whereas SelS silencing rendered them susceptible to the MRSA-induced damage. Mechanistically, neutrophils cultured under low-Se conditions showed reduced SelS expression and released pathological NET DNA upon MRSA infection, which directly triggered intestinal epithelial pyroptosis and barrier disruption. These findings provide a mechanistic basis for Se-based nutritional intervention in MRSA-associated enteritis and offer potential therapeutic targets for nonantibiotic strategies.