Chronic and Repeated Chlamydophila pneumoniae Lung Infection can Result in Increasing IL-4 Gene Expression and Thickness of Airway Subepithelial Basement Membrane in Mice

Abstract

Chlamydophila pneumoniae infection has been associated with several pulmonary and cardiac diseases. However, it has not been explored for its ability to activate the same immunopathologic mechanisms of asthma, namely, a predominant Th2 immune response and structural changes that are termed airway remodeling. This study evaluated immune responses in the lung and airway pathology of BALB/c mice with chronic and repeated C. pneumoniae infections. Methods: Mice were inoculated intranasally with 5 × 106 inclusion-forming units of C. pneumoniae TWAR strain, and re-inoculated at 14 and 42 days after the primary inoculation. Cytokine gene expression in bronchoalveolar lavage (BAL) cells was analyzed by RT-PCR on day 70. Airway pathology was also evaluated by morphometric measurements. Results: A significant increase of interleukin (IL)-4 mRNA was detected in BAL cells in infected mice, and a significant increase in subepithelial basement membrane thickness of the airways was also noted in infected mice as compared with control mice (8.95 ± 0.28 μm vs. 5.54 ± 0.22 μm, p < 0.0001). We further analyzed the correlation between IL-4 cytokine expression and the increased subepithelial basement membrane thickness of airways in infected mice. We found that mice with increased IL-4 mRNA expression had significant increases in the thickness of subepithelial basement membrane as compared with mice without increased IL-4 mRNA expression (9.87 ± 0.51 μm vs. 6.49 ± 0.52 μm, p < 0.0001). Conclusion: It is believed that our results demonstrated for the first time that chronic and repeated infections with C. pneumoniae increased IL-4 gene expression and thickness of airway subepithelial basement membrane in mice.

Keywords

• airway remodeling
• Chlamydophila pneumoniae
• interleukin-4