Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

EMBO Molecular Medicine
Maiko de KerckhoveRyoichi Mori

Abstract

Argonaute 2 bound mature microRNA (Ago2-miRNA) 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 inflammation-related Ago2-miRNAs (miR-139-5p, miR-142-3p, miR-142-5p, and miR-223) and show that miR-223 is critical for infection control. miR-223Y/- mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of Staphylococcus aureus-infected wounds. We also showed that the expression of miR-223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/--derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus-infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.

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Citations

Sep 19, 2018·EMBO Molecular Medicine·Paul Hiebert, Sabine Werner
Oct 17, 2019·Frontiers in Immunology·Matthias Bartneck, Jing Wang
Jun 10, 2020·IUBMB Life·Rasoul MirzaeiRasoul Yousefimashouf
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Aug 31, 2020·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Xin MaZubin Zhou

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Methods Mentioned

BETA
antisense oligodeoxynucleotides
immunoprecipitation
bioluminescence
ELISA
fluorescence imaging
PMA
confocal microscopy
ChIP
GTPase
biopsy

Software Mentioned

GraphPad Prism
NIS
IMARIS
Living Image
Ensembl Genome Browser
Strand NGS
Photoshop CC
Elements C
AR

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