Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation

Etienne Meunier (1, 2) , Agnès Coste (1, 2) , David Olagnier (1, 2) , Hélène Authier (1, 2) , Lise Lefèvre (1, 2) , Christophe Dardenne (1, 2) , José Bernad (1, 2) , Maryse Béraud (1, 2) , Emmanuel Flahaut (3) , Bernard Pipy (1, 2)

1 Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses
2 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
3 CIRIMAT - Centre interuniversitaire de recherche et d'ingenierie des matériaux

Because of their outstanding physical properties, carbon nanotubes (CNTs) are promising new materials in the field of nanotechnology. It is therefore imperative to assess their adverse effects on human health. Monocytes/macrophages that recognize and eliminate the inert particles constitute the main target of CNTs. In this article, we report our finding that double-walled CNTs (DWCNTs) synergize with Toll-like receptor agonists to enhance IL-1β release in human monocytes. We show that DWCNTs-induced IL-1β secretion is exclusively linked to caspase-1 and to Nlrp3 inflammasome activation in human monocytes. We also establish that this activation requires DWCNTs phagocytosis and potassium efflux, but not reactive oxygen specied (ROS) generation. Moreover, inhibition of lysosomal acidification or cathepsin-B activation reduces DWCNT-induced IL-1β secretion, suggesting that Nlrp3 inflammasome activation occurs via lysosomal destabilization. Thus, DWCNTs present a health hazard due to their capacity to activate Nlrp3 inflammasome, recalling the inflammation caused by asbestos and hence demonstrating that they should be used with caution.

Mots clés: Double-walled carbon nanotubes; Human monocytes; Nlrp3 inflammasome; IL-1β; Inflammation

Domaines: Maladies infectieuses; Matériaux

Etienne Meunier, Agnès Coste, David Olagnier, Hélène Authier, Lise Lefèvre, et al.. Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation. Nanomedicine: Nanotechnology, Biology and Medicine, 2012, vol. 8, pp. 987-995. ⟨10.1016/j.nano.2011.11.004⟩. ⟨hal-00857489⟩