Streptococcus pneumoniae induces broad alterations in mitochondrial functions in human airway epithelial cells

Abstract

Background: Metabolic changes in airway epithelial cells have been implicated in the complex pathogenesis of COPD. Bacterial infections are known to cause acute exacerbation in a group of COPD patients. However, the contribution of pathogens to the development of mitochondrial alterations in airway epithelial cells remains elusive and was investigated in frame of this study. Methods: Human bronchial epithelial cells (16HBE) were co-cultured with Streptococcus pneumoniae (Sp) serotype 19F. The impact of pathogen exposure on the mitochondrial oxidative burden was examined by MitoSox using FACS and the expression of ROS adaptor protein p66 was quantified by immunoblotting. The effect of Sp on mitochondrial membrane potential (ΔΨmt) was analyzed by measuring fluorescence intensity of JC-1 dye. The impact of Sp exposure on mitochondrial dynamics was evaluated by quantifying expression of genes and proteins involved in fission and fusion processes as well as mitochondrial biogenesis. Results: Sp co-cultivation induced oxidative stress in 16HBE cells as indicated by elevated mtROS levels as well as p66 protein expression and in line with this, Sp challenge reduced ΔΨmt. Moreover, Spin vitro infection attenuated fusion factors mitofusion 1 and mitofusion 2, while enhancing fission gene and protein expressions of dynamin-related protein 1 as well as accelerating mitochondrial biogenesis. Conclusions: Together, these results indicate that Sp alters various mitochondrial functions within airway epithelial cells. Future studies are needed to decipher in more detail the specific role of these Sp-induced mitochondrial alterations in the pathogenesis of COPD exacerbations.