Polyene macrolide antifungal drugs trigger interleukin-1β secretion by activating the NLRP3 inflammasome.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_D8F10A400F2B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Polyene macrolide antifungal drugs trigger interleukin-1β secretion by activating the NLRP3 inflammasome.
Périodique
PLoS One
Auteur⸱e⸱s
Darisipudi M.N., Allam R., Rupanagudi K.V., Anders H.J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Volume
6
Numéro
5
Pages
e19588
Langue
anglais
Résumé
The use of antimycotic drugs in fungal infections is based on the concept that they suppress fungal growth by a direct killing effect. However, amphotericin and nystatin have been reported to also trigger interleukin-1β (IL-1β) secretion in monocytes but the molecular mechanism is unknown. Here we report that only the polyene macrolides amphotericin B, nystatin, and natamycin but none of the tested azole antimycotic drugs induce significant IL-1β secretion in-vitro in dendritic cells isolated from C57BL/6 mouse bone marrow. IL-1β release depended on Toll-like receptor-mediated induction of pro-IL-1β as well as the NLRP3 inflammasome, its adaptor ASC, and caspase-1 for enzymatic cleavage of pro-IL-1β into its mature form. All three drugs induced potassium efflux from the cells as a known mechanism for NLRP3 activation but the P2X7 receptor was not required for this process. Natamycin-induced IL-1β secretion also involved phagocytosis, as cathepsin activation as described for crystal-induced IL-1β release. Together, the polyene macrolides amphotericin B, nystatin, and natamycin trigger IL-1β secretion by causing potassium efflux from which activates the NLRP3-ASC-caspase-1. We conclude that beyond their effects on fungal growth, these antifungal drugs directly activate the host's innate immunity.
Mots-clé
Amphotericin B/pharmacology, Animals, Antifungal Agents/pharmacology, Carrier Proteins/metabolism, Caspase 1/metabolism, Cytoskeletal Proteins/metabolism, Dendritic Cells/cytology, Dendritic Cells/drug effects, Immunity, Innate, Immunoblotting, Inflammasomes/drug effects, Interleukin-1beta/secretion, Macrolides/pharmacology, Macrophages/cytology, Macrophages/drug effects, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes/cytology, Monocytes/drug effects, Natamycin/pharmacology, Nystatin/pharmacology, Phagocytosis/drug effects, Potassium/metabolism, Signal Transduction, Toll-Like Receptors
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/10/2011 13:18
Dernière modification de la notice
20/08/2019 15:58
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