Open AccessTargeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds
Author(s) -
Kerckhove Maiko,
Tanaka Katsuya,
Umehara Takahiro,
Okamoto Momoko,
Kanematsu Sotaro,
Hayashi Hiroko,
Yano Hiroki,
Nishiura Soushi,
Tooyama Shiho,
Matsubayashi Yutaka,
Komatsu Toshimitsu,
Park Seongjoon,
Okada Yuka,
Takahashi Rina,
Kawano Yayoi,
Hanawa Takehisa,
Iwasaki Keisuke,
Nozaki Tadashige,
Torigoe Hidetaka,
Ikematsu Kazuya,
Suzuki Yutaka,
Tanaka Katsumi,
Martin Paul,
Shimokawa Isao,
Mori Ryoichi
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809024
Subject(s) - staphylococcus aureus , microbiology and biotechnology , methicillin resistant staphylococcus aureus , chemistry , bacteria , biology , genetics
Argonaute 2 bound mature micro RNA (Ago2‐mi RNA ) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNA s. In this study, we identified four wound inflammation‐related Ago2‐mi RNA s ( miR‐139‐5p , miR‐142‐3p , miR‐142‐5p , and miR‐223 ) and show that miR‐223 is critical for infection control. miR‐223 Y /− 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‐223 Y /− ‐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.