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Increased Susceptibility to RSV Infection by Exposure to Inhaled Diesel Engine Emissions

Asthma and Pulmonary Immunology Program, and Experimental Toxicology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico

Address correspondence to: Kevin S. Harrod, Ph.D., Asthma and Pulmonary Immunology, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108. E-mail: kharrod{at}lrri.org

Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 µg/m³ particulate matter (PM) or 1,000 µg/m³ PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.

Abbreviations: bronchoalveolar lavage fluid, BALF • Clara cell secretory protein, CCSP • diesel engine emissions, DEE • enzyme-linked immunosorbent assay, ELISA • interferon-, IFN- • mucous cell metaplasia, MCM • plaque-forming units, pfu • particulate matter, PM • respiratory syncytial virus, RSV • tumor necrosis factor-, TNF-

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