Molecular Mechanism for Particulate Matter Exacerbates Bacteria-Induced Pulmonary Inflammation

Streptococcus pneumoniae (also refer to as pneumococcus) is one of the most common human airway pathogens that cause life-threatening infections. Ambient fine particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM2.5) is known to significantly contribute to respiratory diseases. PM2.5-induced airway inflammation may decrease innate immune defenses against bacterial infection. However, there is currently limited information available regarding the effect of PM2.5 on molecular interactions between pneumococcus and macrophages. Our current results showed that PM2.5 dampens macrophage phagocytic activity and reduces pneumococcal clearance, indicating that PM2.5 acts as a powerful coordinator for modulating innate immunity. As macrophages harbor potent impact on defense against pathogen infections, this proposal hypothesizes that PM2.5 subverts the airway innate immunity to increase pneumococcal infectivity. Therefore, this proposal will (i) investigate how PM2.5 influences inflammatory mediators against pneumococcal infection; (ii) study the impact of PM2.5 on pneumococcus-induced macrophage polarizations; (iii) explore how PM2.5 dampens pneumococcus-induced chemokine production. This proposal combined molecular-based and animal studies will unveil the mechanisms how PM2.5 impairs macrophage activity to enhance pneumococcal infectivity, resulting in aggravation of pulmonary pathogenesis.

Project ID:PC10907-1532
External Project ID:MOST109-2320-B182-029-MY3