3 years ago

Silver Nanoparticles Impair Retinoic Acid-Inducible Gene I-Mediated Mitochondrial Antiviral Immunity by Blocking the Autophagic Flux in Lung Epithelial Cells

Silver
Nanoparticles Impair Retinoic Acid-Inducible
Gene I-Mediated Mitochondrial Antiviral Immunity by Blocking
the Autophagic Flux in Lung Epithelial Cells
Brigitte Solhonne, Jean-Michel Sallenave, Arnaud Mailleux, Pika Miklavc, Paul Dietl, Rémi Le Borgne, Alexandra Dieu, Sena Hamadi, Joel Aerts, Ignacio Garcia-Verdugo, Devy Diallo, Marjolene Straube, Francois Rouzet, Berengere Villeret, Xavier Norel
Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as an alternative to antivirals to treat human infectious diseases, especially influenza virus infections 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 an influenza virus infection of lung epithelial cells, that AgNPs down-regulated influenza induced CCL-5 and -IFN-β release (two cytokines important in antiviral 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 antiviral 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 antiviral responses and up-regulation of IL-8-dependent antibacterial responses) may have practical implications for their use in the clinic.

Publisher URL: http://dx.doi.org/10.1021/acsnano.7b06934

DOI: 10.1021/acsnano.7b06934

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