Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

Background: Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with Klebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice.Methods: Male and female C57BL/6 mice were exposed to O₃ or to filtered air (FA) (control) and then infected intratracheally with K. pneumoniae bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h.Results: 1) Both male and female mice exposed to O₃ are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O₃ exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.Conclusion: O₃ exposure reduces the ability of mice to survive K. pneumoniae infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.