Altered cytokine release of airway epithelial cells in vitro by combinations of Respiratory Syncytial Virus, Streptococcus pneumoniae, Printex 90 and Diesel Exhaust Particles

Abstract

Air pollution exposure has been linked to an increased severity of respiratory infections. Studying the cellular mechanisms behind a potential interaction between biological infectious agents, like viruses or bacteria, and the chemical constituent of air pollution could provide more understanding of this finding. In vitro models allow assessment of the mechanisms leading to such increased severity of respiratory infections. The response of primary respiratory bronchial epithelial cells was investigated after combined exposure to biological agents (Respiratory Syncytial Virus (RSV), the bacterium Streptococcus pneumoniae), and chemical agents (Printex 90 or diesel exhaust particles (DEP)). Multiple combinations of exposures to these agents were tested and the effect on cell viability and cytotoxicity were assessed. The secretion levels of 24 pro- and anti-inflammatory cytokines were assessed at levels that did not cause cytotoxicity. Infection with RSV resulted in decreased metabolic activity and an increase in cytokine levels compared to the other exposures. Exposures to the bacterial and chemical agents, in addition to an RSV infection, resulted in a further increase in cytokine levels. We found a cluster of cytokines that responded similarly to the performed exposures which were CXCR3 ligands CXCL9, CXCL10 and CXCL11 and CCR5 ligand CCL5. Even though the data suggests that combined exposures result in a further increase of cytokine levels, this was not confirmed by statistical analysis. Together, this information may help to understand the cellular effects of combined exposure in an in vitro setting and the biological responses to these exposures in vivo.