The online version of this article (https://doi.org/10.1186/s12985-017-0909-z) contains supplementary material, which is available to authorized users.
Numerous toxicological studies have focused on injury caused by exposure to single types of nanoparticles, but few have investigated how such exposures impact a host’s immune response to pathogen challenge. Few studies have shown that nanoparticles can alter a host’s response to pathogens (chiefly bacteria) but there is even less knowledge of the impact of such particles on viral infections. In this study, we performed experiments to investigate if exposure of mice to single-walled carbon nanotubes (SWCNT) alters immune mechanisms and viral titers following subsequent influenza A virus (IAV) infection.
Male C57BL/6 mice were exposed to 20 μg of SWCNT or control vehicle by intratracheal instillation followed by intranasal exposure to 3.2 × 104 TCID50 IAV or PBS after 3 days. On day 7 mice were euthanized and near-infrared fluorescence (NIRF) imaging was used to track SWCNT in lung tissues. Viral titers, histopathology, and mRNA expression of antiviral and inflammatory genes were measured in lung tissue. Differential cell counts and cytokine levels were quantified in bronchoalveolar lavage fluid (BALF).
Viral titers showed a 63-fold increase in IAV in SWCNT + IAV exposed lungs compared to the IAV only exposure. Quantitation of immune cells in BALF indicated an increase of neutrophils in the IAV group and a mixed profile of lymphocytes and neutrophils in SWCNT + IAV treated mice. NIRF indicated SWCNT remained in the lung throughout the experiment and localized in the junctions of terminal bronchioles, alveolar ducts, and surrounding alveoli. The dual exposure exacerbated pulmonary inflammation and tissue lesions compared to SWCNT or IAV single exposures. IAV exposure increased several cytokine and chemokine levels in BALF, but greater levels of IL-4, IL-12 (P70), IP-10, MIP-1, MIP-1α, MIP-1β, and RANTES were evident in the SWCNT + IAV group. The expression of tlr3, ifnβ1, rantes, ifit2, ifit3, and il8 was induced by IAV alone but several anti-viral targets showed a repressed trend (ifits) with pre-exposure to SWCNT.
These findings reveal a pronounced effect of SWCNT on IAV infection in vivo as evidenced by exacerbated lung injury, increased viral titers and several cytokines/chemokines levels, and reduction of anti-viral gene expression. These results imply that SWCNT can increase susceptibility to respiratory viral infections as a novel mechanism of toxicity.
Additional file 1: Table S1A. All mouse weight during 7-day experiment in grams (Mean ± SD). S1B. All mouse weight loss during 7-day experiment as % change from day 0 (Mean ± SD). Table S2. Primer sets used in this study. Figure. S1. Characterization of SWCNT. Hydrodynamic radii plot of SG65i dialyzed SWCNT used in all experiments. All experiments were performed at 37 oC. Figure S2. NIRF of lung tissues among animals in control and IAV only group. Mouse lung H&E stained tissue sections from a (A) control and (B) IAV exposed animal and corresponding NIRF image, 400X. (PDF 879 kb)
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- Single-walled carbon nanotubes modulate pulmonary immune responses and increase pandemic influenza a virus titers in mice
Sara T. Humes
Julia C. Loeb
Sarah E. Robinson
Joseph H. Bisesi Jr
Navid B. Saleh
William L. Castleman
John A. Lednicky
- BioMed Central
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