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

ΤίτλοςImmunomodulatory Role of Clarithromycin in Acinetobacter baumannii Infection via Formation of Neutrophil Extracellular Traps.
Publication TypeJournal Article
Year of Publication2015
AuthorsKonstantinidis T, Kambas K, Mitsios A, Panopoulou M, Tsironidou V, Dellaporta E, Kouklakis G, Arampatzioglou A, Angelidou I, Mitroulis I, Skendros P, Ritis K
JournalAntimicrobial agents and chemotherapy
Volume60
Issue2
Pagination1040-8
Date Published2015 Dec 7
ISSN0066-4804
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.

URLhttp://aac.asm.org/cgi/pmidlookup?view=long&pmid=26643338
DOI10.1128/AAC.02063-15
Short TitleAntimicrob Agents Chemother