Diesel exhaust enhances influenza virus infections in respiratory epithelial cells

Toxicol Sci. 2005 Jun;85(2):990-1002. doi: 10.1093/toxsci/kfi141. Epub 2005 Mar 16.

Abstract

Several factors, such as age and nutritional status, can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects and replicates in respiratory epithelial cells, which are also a major targets for inhaled DE. Using in vitro models of human respiratory epithelial cells, we determined the effects of an aqueous-trapped solution of DE (DE(as)) on influenza infections. Differentiated human nasal and bronchial epithelial cells, as well as A549 cells, were exposed to DE(as) and infected with influenza A/Bangkok/1/79. DE(as) enhanced the susceptibility to influenza virus infection in all cell models and increased the number of influenza-infected cells within 24 h post-infection. This was not caused by suppressing antiviral mediator production, since interferon (IFN) beta levels, IFN-dependent signaling, and IFN-stimulated gene expression were also enhanced by exposure to DE(as). Many of the adverse effects induced by DE exposure are mediated by oxidative stress. Exposure to DE(as) used in these studies generated oxidative stress in respiratory epithelial cells, and addition of the antioxidant glutathione-ethylester (GSH-ET) reversed the effects of DE(as) on influenza infections. Furthermore, DE(as) increased influenza virus attachment to respiratory epithelial cells within 2 h post-infection. Taken together, the results presented here suggest that in human respiratory epithelial cells oxidative stress generated by DE(as) increases the susceptibility to influenza infection and that exposure to DE(as) increases the ability of the virus to attach to and enter respiratory epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blotting, Western
  • Bronchi / cytology
  • Cell Line
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Glutathione / pharmacology
  • Humans
  • Immunohistochemistry
  • Influenza A virus
  • Influenza, Human / pathology*
  • Influenza, Human / virology
  • Interferon-gamma / biosynthesis
  • Oxidative Stress / drug effects
  • Promoter Regions, Genetic / genetics
  • RNA / biosynthesis
  • RNA / genetics
  • Respiratory Mucosa / pathology*
  • Respiratory Mucosa / virology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vehicle Emissions / toxicity*

Substances

  • Vehicle Emissions
  • RNA
  • Interferon-gamma
  • Glutathione