Repeated exposures to PM2.5 alter the mitochondria and the influenza-mediated interferon response in an air-liquid interface bronchial epithelium

Humans are exposed to various contaminants, including fine atmospheric particles (PM_2.5) and respiratory viruses. Epidemiological studies have demonstrated a positive association between exposure to PM_2.5 and the severity of viral infections, including those caused by influenza viruses. Nevertheless, there is a paucity of in vitro studies investigating the underlying mechanisms, especially in the context of repeated exposures to PM_2.5, which more realistically reflect human exposure. This study aimed to perform repeated exposures to PM_2.5 collected in Paris on an in vitro bronchial epithelium model at the air-liquid interface (ALI) prior to infection with influenza A virus (IAV), and to assess modulations of antiviral responses. This work firstly demonstrated particle internalisation and a sustained pro-inflammatory response during repeated exposures to PM_2.5. Repeated exposures to PM_2.5 prior to IAV infection revealed a downregulation of the interferon (IFN) pathway without modulation of the pro-inflammatory response. Furthermore, mitochondrial dysfunction was observed following repeated PM_2.5 exposures, as well as an accumulation of autophagic vesicles and p62 protein. This suggests the involvement of mitochondrial alteration and/or blockage of autophagic flux in the modulation of the IFN signalling pathway, and warrants further investigation.