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.