Format

Send to

Choose Destination
Nanotoxicology. 2019 Nov;13(9):1176-1196. doi: 10.1080/17435390.2019.1645903. Epub 2019 Sep 27.

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

Author information

1
Department of Environmental and Global Health, Center for Environmental and Human Toxicology and Emerging Pathogens Institute, University of Florida , Gainesville , FL , USA.
2
Department of Department of Civil, Architectural, and Environmental Engineering, University of Texas Austin , Austin , TX , USA.
3
Department of Biochemistry & Molecular Biology, University of Florida , Gainesville , FL , USA.
4
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida , Gainesville , FL , USA.

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, IFN╬▓1, 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.

KEYWORDS:

Single-walled carbon nanotubes; infection; influenza A virus; innate immune response; oxidative stress

PMID:
31328592
PMCID:
PMC6803130
[Available on 2020-11-01]
DOI:
10.1080/17435390.2019.1645903

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center