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

• Published in: Antimicrobial agents and chemotherapy 2016-02, Vol.60 (2), p.1040-1048
• Main Authors: Konstantinidis, Theocharis, Kambas, Konstantinos, Mitsios, Alexandros, Panopoulou, Maria, Tsironidou, Victoria, Dellaporta, Erminia, Kouklakis, Georgios, Arampatzioglou, Athanasios, Angelidou, Iliana, Mitroulis, Ioannis, Skendros, Panagiotis, Ritis, Konstantinos
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - pathogenicity; Acinetobacter Infections; Acinetobacter Infections - drug therapy; Acinetobacter Infections - immunology; Acinetobacter Infections - pathology; Adult; Anti-Bacterial Agents - immunology; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides; Autophagy - drug effects; Biologic Response Modifiers; Case-Control Studies; Cathelicidins - metabolism; Clarithromycin; Clarithromycin - immunology; Clarithromycin - pharmacology; Extracellular Traps; Extracellular Traps - drug effects; Female; Gastritis - blood; Helicobacter Infections - blood; Helicobacter Infections - microbiology; Humans; Immunologic Factors; Immunologic Factors - immunology; Immunologic Factors - pharmacology; Male; Middle Aged; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - pathology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.02063-15

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.