title: Immunomodulatory Role of Clarithromycin in Acinetobacter baumannii Infection via Formation of Neutrophil Extracellular Traps.
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.
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Theocharis
authors.initials: T
authors.lastname: Konstantinidis
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kambas
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Mitsios
authors.affiliation: Laboratory of Microbiology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Panopoulou
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Victoria
authors.initials: V
authors.lastname: Tsironidou
authors.affiliation: Gastrointestinal Endoscopy Unit, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Erminia
authors.initials: E
authors.lastname: Dellaporta
authors.affiliation: Gastrointestinal Endoscopy Unit, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kouklakis
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Arampatzioglou
authors.affiliation: Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Iliana
authors.initials: I
authors.lastname: Angelidou
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.affiliation: 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.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Skendros
authors.affiliation: 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.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D040981:Acinetobacter baumannii / Q000472:pathogenicity; D000328:Adult; D000900:Anti-Bacterial Agents / Q000276:immunology / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001343:Autophagy / Q000187:drug effects; D016022:Case-Control Studies; D054804:Cathelicidins / Q000378:metabolism; D017291:Clarithromycin / Q000276:immunology / Q000494:pharmacology*; D065206:Extracellular Traps / Q000187:drug effects*; D005260:Female; D005756:Gastritis / Q000097:blood; D016481:Helicobacter Infections / Q000097:blood / Q000382:microbiology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007155:Immunologic Factors; D017291:Clarithromycin