Histopathologic evaluation of lung and extrapulmonary tissues show sex differences in klebsiella pneumoniae - infected mice under different exposure conditions

It has been shown that female mice with pneumonia have a survival advantage over males, but this is reversed if ozone exposure precedes infection. The purpose of this study was to investigate factors that underlie these observations, by studying histopathologic changes in lung and extrapulmonary (spleen and liver) tissues after ozone or filtered air (FA) exposure followed by pulmonary bacterial infection. Male and female wild type C57BL/6J mice were exposed to ozone or FA, then anesthetized and infected intratracheally with Klebsiella pneumoniae bacteria. Tissues (lung, spleen, and liver) were subjected to histopathologic analysis at 48 h post-infection. We found that after infection, 1) the severity of inflammation was higher, the affected area of the lung was larger, and spleen red pulp myelopoiesis was lower in ozone-exposed mice compared to FA-exposed animals in both sexes; 2) more pronounced extrapulmonary lesions (in liver and spleen) were observed in FA-exposed males compared to FA-exposed females; and 3) excessive lung inflammatory response was detected in ozone-exposed females compared to ozone-exposed males. We concluded that different risk factors contribute to the differential outcome of pneumonia between sexes in the presence or absence of ozone-induced oxidative stress. In specific, the excessive lung inflammation and higher risk for extrapulmonary lesions in ozone-exposed infected females and in FA-exposed infected males appear to play, respectively, a dominant role in the previously observed respective survival outcomes.