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Hydroxyl functionalized multi-walled carbon nanotubes modulate immune responses without increasing 2009 pandemic influenza A/H1N1 virus titers in infected mice.

Abstract
Growing use of carbon nanotubes (CNTs) have garnered concerns regarding their association with adverse health effects. Few studies have probed how CNTs affect a host's susceptibility to pathogens, particularly respiratory viruses. We reported that exposure of lung cells and mice to pristine single-walled CNTs (SWCNTs) leads to significantly increased influenza virus H1N1 strain A/Mexico/4108/2009 (IAV) titers in concert with repressed antiviral immune responses. In the present study, we investigated if hydroxylated multi-walled CNTs (MWCNTs), would result in similar outcomes. C57BL/6 mice were exposed to 20 μg MWCNTs on day 0 and IAV on day 3 and samples were collected on day 7. We investigated pathological changes, viral titers, immune-related gene expression in lung tissue, and quantified differential cell counts and cytokine and chemokine levels in bronchoalveolar lavage fluid. MWCNTs alone caused mild inflammation with no apparent changes in immune markers whereas IAV alone presented typical infection-associated inflammation, pathology, and titers. The co-exposure (MWCNTs + IAV) did not alter titers or immune cell profiles compared to the IAV only but increased concentrations of IL-1β, TNFα, GM-CSF, KC, MIPs, and RANTES and inhibited mRNA expression of Tlr3, Rig-i, Mda5, and Ifit2. Our findings suggest MWCNTs modulate immune responses to IAV with no effect on the viral titer and modest pulmonary injury, a result different from those reported for SWCNT exposures. This is the first study to show that MWCNTs modify cytokine and chemokine responses that control aspects of host defenses which may play a greater role in mitigating IAV infections.
AuthorsHao Chen, Sara T Humes, Melanie Rose, Sarah E Robinson, Julia C Loeb, Indu V Sabaraya, L Cody Smith, Navid B Saleh, William L Castleman, John A Lednicky, Tara Sabo-Attwood
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 404 Pg. 115167 (10 01 2020) ISSN: 1096-0333 [Electronic] United States
PMID32771490 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • Nanotubes, Carbon
Topics
  • Animals
  • Gene Expression Regulation (drug effects, immunology)
  • Influenza A Virus, H1N1 Subtype
  • Lung Injury (chemically induced)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanotubes, Carbon
  • Orthomyxoviridae Infections (immunology, virology)

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