Abstract
BACKGROUND: Epidemiological studies have shown that urban particulate matter (PM) increases the risk of respiratory infection. However, the underlying mechanisms are poorly understood. PM has been postulated to suppress the activation of airway epithelial innate defence in response to infection. METHODS: The effects of PM on antibacterial defence were studied using an in vitro infection model. The levels of antimicrobial peptides were measured using RT-PCR and ELISA. In addition to performing colony-forming unit counts and flow cytometry, confocal microscopy was performed to directly observe bacterial invasion upon PM exposure. RESULTS: We found that PM PM increased bacterial invasion by impairing the induction of β-defensin-2 (hBD-2), but not the other antimicrobial peptides (APMs) secreted by airway epithelium. PM further increases bacteria-induced ROS production, which is accompanied by an accelerated cell senescence and a decrease in bacteria-induced hBD-2 production, and the antioxidant NAC treatment attenuates these effects. The PM exposure further upregulated the expression of IL-8 but downregulated the expression of IL-13 upon infection. CONCLUSIONS: PM promotes bacterial invasion of airway epithelial cells by attenuating the induction of hBD-2 via an oxidative burst. These findings associate PM with an increased susceptibility to infection. These findings provide insight into the underlying mechanisms regarding the pathogenesis of particulate matter.