Effect of diesel exhaust on the host response to respiratory viral infection: involvement of toll-like receptor 3

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  • March 20, 2019
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  • Ciencewicki, Jonathan Michael
    • Affiliation: School of Medicine, Curriculum in Toxicology
Abstract
  • Adverse effects resulting from exposure to air pollutants have become an increasing problem worldwide. Particularly levels of air pollutants have been associated with increases in the susceptibility and response to many respiratory diseases. Of the numerous air pollutants, diesel exhaust (DE) has become a major concern since it can account for a significant amount of the pollutants generated by motor vehicles in many areas. Previous results in our laboratory have demonstrated that prior exposure of respiratory epithelial cells to DE enhances the susceptibility to influenza infections. In this work, these results were confirmed and expanded upon both in vitro and in vivo. The effects of DE on the expression and signaling of toll-like receptor 3 (TLR3), which has previously shown to be needed for a complete innate immune response to influenza infections as well as other respiratory viral infections, were examined as well as mechanistic aspects involved in the observed effects. Increased expression and signaling of TLR3 was observed in respiratory epithelial cells exposed to DE prior to infection with influenza, resulting in an enhancement of the influenza-induced inflammatory and interferon (IFN) responses. A positive-feedback loop involving type I IFNs and DE-induced effects on epithelial cell tight junctional complexes played a role in the observed effects. In vivo exposure of mice to DE enhanced the susceptibility to influenza infections and decreased expression of surfactant proteins A and D, which are an important part of the innate immune defense against influenza and other respiratory viruses. Together, these results demonstrate that exposure to an oxidant air pollutant, such as diesel exhaust, can enhance the susceptibility and response to respiratory viral infection and elucidate potential mechanisms behind some of these effects.
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  • In Copyright
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  • Jaspers, Ilona
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  • Open access
Date uploaded
  • October 19, 2010

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