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Single-walled carbon nanotubes repress viral-induced defense pathways through oxidative stress.

Authors :
Chen H
Humes ST
Robinson SE
Loeb JC
Sabaraya IV
Saleh NB
Khattri RB
Merritt ME
Martyniuk CJ
Lednicky JA
Sabo-Attwood T
Source :
Nanotoxicology [Nanotoxicology] 2019 Nov; Vol. 13 (9), pp. 1176-1196. Date of Electronic Publication: 2019 Sep 27.
Publication Year :
2019

Abstract

Exposure of lung cells in vitro or mice to single-walled carbon nanotubes (SWCNTs) directly to the respiratory tract leads to a reduced host anti-viral immune response to infection with influenza A virus H1N1 (IAV), resulting in significant increases in viral titers. This suggests that unintended exposure to nanotubes via inhalation may increase susceptibility to notorious respiratory viruses that carry a high social and economic burden globally. However, the molecular mechanisms that contribute to viral susceptibility have not been elucidated. In the present study, we identified the retinoic acid-induced gene I (RIG-I) like receptors (RLRs)/mitochondrial antiviral signaling (MAVS) pathway as a target of SWCNT-induced oxidative stress in small airway epithelial cells (SAEC) that contribute to significantly enhanced influenza viral titers. Exposure of SAEC to SWCNTs increases viral titers while repressing several aspects of the RLR pathway, including mRNA expression of key genes (e.g. IFITs , RIG-I , MDA5 , IFNβ1 , CCL5 ). SWCNTs also reduce mitochondrial membrane potential without altering oxygen consumption rates. Our findings also indicate that SWCNTs can impair formation of MAVS prion-like aggregates, which is known to impede downstream activation of the RLR pathway and hence the transcriptional production of interferon-regulated anti-viral genes and cytokines. Furthermore, application of the antioxidant NAC alleviates inhibition of gene expression levels by SWCNTs, as well as MAVS signalosome formation, and increased viral titers. These data provide evidence of targeted impairment of anti-viral signaling networks that are vital to immune defense mechanisms in lung cells, contributing to increased susceptibility to IAV infections by SWCNTs.

Details

Language :
English
ISSN :
1743-5404
Volume :
13
Issue :
9
Database :
MEDLINE
Journal :
Nanotoxicology
Publication Type :
Academic Journal
Accession number :
31328592
Full Text :
https://doi.org/10.1080/17435390.2019.1645903