Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

• Published in: Particle and fibre toxicology 2014-10, Vol.11 (1), p.57-57, Article 57
• Main Authors: Lee, Greg I, Saravia, Jordy, You, Dahui, Shrestha, Bishwas, Jaligama, Sridhar, Hebert, Valerie Y, Dugas, Tammy R, Cormier, Stephania A
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - drug effects; Animals; Animals, Newborn; Children & youth; Combustion; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Disease; Experiments; Exposure; Flow cytometry; Free radicals; Free Radicals - toxicity; Glutathione - metabolism; Health aspects; Health sciences; Humans; Immune response; Infants (Newborn); Infections; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza virus; Inhalation Exposure - adverse effects; Lung - drug effects; Lung - immunology; Lung - physiopathology; Lung - virology; Lungs; Mice; Mice, Inbred C57BL; Mice, Transgenic; Morbidity; Neonates; Orthomyxoviridae Infections - chemically induced; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - physiopathology; Orthomyxoviridae Infections - virology; Oxidative stress; Oxidative Stress - drug effects; Particulate emissions; Particulate matter; Particulate Matter - toxicity; Peak load; Respiratory diseases; Risk Assessment; Rodents; Stresses; Studies; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - virology; Time Factors; Variance analysis; Viral infections; Viral Load
• ISSN: 1743-8977; 1743-8977
• DOI: 10.1186/s12989-014-0057-1

Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Neonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity (% weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2. Neonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects. Neonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.