Silver nanoparticles impair retinoic acid-inducible gene I mediated mitochondrial anti-viral immunity by blocking the autophagic flux in lung epithelial cells

Villeret, B; Dieu, A; Straube, M; Solhonne, B; Miklavc, P; Hamadi, S; Le Borgne, R; Mailleux, A; Norel, X; Aerts, J; Diallo, D; Rouzet, F; Dietl, P; Sallenave, J-M; Garcia-Verdugo, I

Abstract

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as alternative to antivirals to treat human infectious diseases, especially Influenza virus infection where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of Influenza virus infection of lung epithelial cells, that AgNPs down-regulated Influenza induced-CCL-5 and -IFN-β release (two cytokines important in anti-viral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the anti-viral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent anti-viral responses and up-regulation of IL-8 -dependent antibacterial responses) may have practical implications for their use in the clinic.

Citation

Villeret, B., Dieu, A., Straube, M., Solhonne, B., Miklavc, P., Hamadi, S., …Garcia-Verdugo, I. (2018). Silver nanoparticles impair retinoic acid-inducible gene I mediated mitochondrial anti-viral immunity by blocking the autophagic flux in lung epithelial cells. ACS nano, 12(2), 1188-1202. https://doi.org/10.1021/acsnano.7b06934

• Journal Article Type: Article
• Acceptance Date: Jan 22, 2018
• Online Publication Date: Jan 22, 2018
• Publication Date: Feb 27, 2018
• Deposit Date: Jan 29, 2018
• Publicly Available Date: Jan 22, 2019
• Journal: ACS Nano
• Print ISSN: 1936-0851
• Electronic ISSN: 1936-086X
• Publisher: American Chemical Society
• Volume: 12
• Issue: 2
• Pages: 1188-1202
• DOI: https://doi.org/10.1021/acsnano.7b06934
• Publisher URL: http://dx.doi.org/10.1021/acsnano.7b06934
• Related Public URLs: http://pubs.acs.org/journal/ancac3
• Additional Information: Additional Information : This document is the Accepted Manuscript version of a Published Work that appears in final form in ACS Nano, copyright © American Chemical Society. To access the final edited and published work see official URL link above.; Funders : Chancellerie des Universités de Paris;National Agency of Research (France)