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.