Diesel Exhaust Enhances Influenza Virus Infections in Respiratory Epithelial Cells

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) β 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.

influenza, diesel exhaust, in vitro, epithelial cells, oxidative stress