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Antimicrob Agents Chemother. 2015 Dec 7;60(2):1040-8. doi: 10.1128/AAC.02063-15. Print 2016 Feb.

Immunomodulatory Role of Clarithromycin in Acinetobacter baumannii Infection via Formation of Neutrophil Extracellular Traps.

Author information

1
Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
2
Laboratory of Microbiology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
3
Gastrointestinal Endoscopy Unit, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
4
Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
5
Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
6
Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece kritis@med.duth.gr.

Abstract

Macrolide antibiotics have been shown to act as immunomodulatory molecules in various immune cells. However, their effect on neutrophils has not been extensively investigated. In this study, we investigated the role of macrolide antibiotics in the generation of neutrophil extracellular traps (NETs). By assessing ex vivo and in vivo NET formation, we demonstrated that clarithromycin is able to induce NET generation both in vitro and in vivo. Clarithromycin utilizes autophagy in order to form NETs, and these NETs are decorated with antimicrobial peptide LL-37. Clarithromycin-induced NETs are able to inhibit Acinetobacter baumannii growth and biofilm formation in an LL-37-dependent manner. Additionally, LL-37 antimicrobial function depends on NET scaffold integrity. Collectively, these data expand the knowledge on the immunomodulatory role of macrolide antibiotics via the generation of LL-37-bearing NETs, which demonstrate LL-37-dependent antimicrobial activity and biofilm inhibition against A. baumannii.

PMID:
26643338
PMCID:
PMC4750671
DOI:
10.1128/AAC.02063-15
[Indexed for MEDLINE]
Free PMC Article

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