Insights into the mechanisms of mitochondria-regulated airway epithelial cell dysfunction upon cigarette smoke extract exposure and pneumococcal infection

Abstract

Cigarette smoking is considered as one of the major risk factors for development of airway diseases, inducing airway epithelial dysfunction, sustained inflammation as well as a decline in lung function. Bacterial and viral infections may aggravate smoke-induced airway diseases by inducing further airway inflammation. Streptococcus pneumoniae (Sp) is one of the most commonly isolated bacteria from the airways during airway diseases that may escalate condition by eliciting further oxidative stress and inflammation. Mitochondria as the central regulator of ROS production were also recently identified to be involved in innate immune responses to the pathogens. Mitochondrial function is impaired in airway epithelial cells of smokers. However, the mechanistic pathways linking mitochondrial dysfunction to airway epithelial innate immune responses and airway epithelial barrier function is still lacking. We found that mitochondrial dysfunction induced by cigarette smoke extract may link to dampen innate immune responses and disrupted epithelial barriers upon Sp infection in the airway epithelium. Mitochondrial dysfunction was reversible by using mitochondrial targeted compounds, which may provide a promising therapeutic strategy to overcome bacterial-induced airway epithelial cell dysfunction.