Carbon nanoparticle-triggered virus reactivation as a link between the inflammatory response to air pollutants and chronic lung disease

Abstract

Particulate air pollution and gammaherpesviruses are omnipresent in human society. These viruses remain in a latent state in the host for life. We have previously shown that pulmonary exposure to carbon nanoparticles (CNPs), a typical component of air pollution can lead to the reactivation of latent murine gammaherpesvirus 68 (MHV-68) in the lungs of mice. Repetitive CNP inhalation scenarios might contribute to the exacerbation of chronic lung diseases (CLD). Here we test whether a repeated CNP exposure triggers additive pulmonary inflammatory effects in the mouse model of MHV-68 reactivation and thereby might contribute to exacerbations of CLDs. Repeated intratracheal dosing of latently MHV-68 infected mice with 50µg CNPs at a time interval of 55 days, caused increased and prolonged BAL lymphocyte numbers in MHV-68 infected and particle treated mice, not observed either in animals infected or nanoparticle treated only. The T-cell dominated lung lymphocyte infiltration was accompanied by increased levels of pulmonary <i>Tnf</i>, <i>Saa3</i> and <i>Spp1</i> gene expression, elevated BAL protein and IgM levels, increased interstitial inflammation, reduction of AT2 cells and increased mean chord length, all together indicating progressive emphysema like alveolar damage and reduced epithelial regeneration. Lung damage furthermore was associated with high serum SAA3 concentrations, suggesting systemic inflammation. These observations suggest that repeated CNP exposure of latently MHV-68 infected lungs leads to a prolonged inflammatory response with alveolar-capillary barrier disruption and potential systemic consequences, which may contribute to the exacerbation of CLDs.