1 research outputs found
Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds
Abstract Argonaute 2 bound mature microRNA (Ago2âmiRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammationârelated Ago2âmiRNAs (miRâ139â5p, miRâ142â3p, miRâ142â5p, and miRâ223) and show that miRâ223 is critical for infection control. miRâ223Y/â mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukinâ6 expression, and markedly improved repair of Staphylococcus aureusâinfected wounds. We also showed that the expression of miRâ223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miRâ223Y/ââderived neutrophils, or miRâ223 antisense oligodeoxynucleotides in S. aureusâinfected wildâtype wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miRâ223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miRâ223 might be of therapeutic benefit for infected wounds in the clinic