In vitro copper nanoparticle exposure increases susceptibility of human lung cells to infection by Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae infection can cause pneumonia and invasive pneumococcal disease and is associated with significant morbidity and death worldwide. Moreover, welders are at increased risk of developing pneumococcal infections; which is thought to be a result of chronic overexposure to metal nanoparticles (NPs) found in welding fumes. To understand how NPs increase susceptibility to pneumococcal infection, we examined NP effects on cell viability, oxidative stress, and inflammation and whether changes in these outcomes sensitize lung cells to adhesion by different serotypes of S. pneumoniae. Using human lung A549 cells we showed that necrosis was the preferred mode of cell death after CuONP exposure, likely a result of the rapid dissolution of CuONPs into toxic copper ions. Moreover, CuONP exposure led to increased production of pro-inflammatory cytokines and increased production of reactive oxygen species to promote A549 cell death. In addition, pneumococcal adhesion was increased in A549 cells after CuONP exposure. However, pre-incubation with the antioxidant N-acetylcysteine prior to CuONP exposure led to decreased cell death as well as diminished pneumococcal adhesion. The autophagy inhibitor wortmannin was also shown to slightly ameliorate the cell death observed after CuONP exposure, however its effect on pneumococcal adhesion remains unknown. Taken together, these results show a possible relationship between oxidative stress, inflammation, cell death, and bacterial adhesion after CuONP exposure. This information is important because understanding the underlying biological mechanisms allows us to better provide the best methods and treatments to prevent or reduce the risks of NP-induced or -exacerbated pneumonia.