Environmentally Relevant Levels of Ozone Enhance Klebsiella pneumoniae Pulmonary Colonization and Cross-Organ Translocation

Ozone (O3) is a major global air pollutant. Recent epidemiological studies have suggested links between O3 exposure and outbreaks of infectious diseases. However, whether environmentally relevant levels of O3 exacerbate the colonization and infection of airborne pathogens remains unclear. This study demonstrated that exposure to environmentally relevant levels of O3 (0.15 and 0.60 ppm) significantly enhanced pulmonary colonization of low-dose Klebsiella pneumoniae (1 × 103 CFU/mouse) in mice, which failed to colonize without O3 exposure. Unexpectedly, in vivo and in vitro coculture experiments with BEAS-2B bronchial epithelial cells demonstrated that O3 exposure also enhanced the ability of K. pneumoniae to penetrate the lung-blood barrier, thereby inducing bacteremia that spread to the liver and caused severe liver injury. O3 exposure reduced the proportions of T cells, B cells, and macrophages in the lungs and altered the expression of key pulmonary genes (Tlr4, Il-18, Traf6, and Tgf-β1) involved in resisting K. pneumoniae colonization. In addition, lipid peroxidation product MDA in plasma acted as a mediator in the signal transmission along the lung-liver axis. This study underscores the critical role of air pollutants in pathogen colonization and infection, emphasizing the urgent need to address air quality to mitigate respiratory health risks.