LAUSR

Epidemiological studies have shown an association between exposure to fine particles (PM2.5) and the severity of respiratory infections such as influenza and COVID-19. PM2.5 and viruses target the bronchial epithelium suggesting that exposure to PM2.5 could make it more susceptible to infections. Our project aims to study the impact of PM2.5 on the severity of influenza virus and decipher the underlying mechanisms. We used a human bronchial epithelium grown at air-liquid interface (ALI) and characterised its responses to a single 24h exposure to PM2.5 at ALI at 5, 10 or 20 µg/cm². Particles induced the expression of the pro-inflammatory cytokines IL-6 and IL-8 as well as IFN-β showing an impact on the antiviral signaling pathway. When bronchial epithelium is infected with influenza virus (murine H3N2) after 24h exposure to PM2.5, there is an increase in LDH activity in the apical secretome associated with a trend towards increased expression of the viral protein M2 as well as an enhanced release of mediators of the antiviral defense (IL-6, IL-8, RANTES), compared to the non-exposed epithelium. These results suggest that pre-exposure to PM2.5 may increase the severity of viral infection in association with an increase of viral replication which needs to be confirmed subsequently by virus titration. Antiviral signaling is now investigated and the effects of repeated exposures of the bronchial epithelium to PM2.5 on the severity of viral infection are also explored.  This work is support by the Foundation for Medical Research, French Environment and Energy Management Agency and DIM Qi2.