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Updated: Sep 26, 2025
Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
Tracking the response to Pseudomonas aeruginosa infection in ozone-induced chronic obstructive pulmonary disease
Lei Han1, Yuning Huang1, Qiang Fu1
1Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) is commonly isolated from the sputum of COPD patients. However, the precise role of P. aeruginosa infection in the progression of COPD, especially its role in altering inflammation remains unclear. Here, we designed mice models of COPD infected with P. aeruginosa (PA) and observed dynamic changes of lung structure, lung inflammatory microenvironment, lung function. After infection, the level of mucus secretion peaked on day 3 and remained higher throughout the study period, and the airway remodeling and emphysema was starkly apparent on day 14 and 21. On day 3, interferon-γ and interleukin (IL)- 5 levels increased rapidly, accompanied by elevated T-bet mRNA expression and CD4+T-bet+ cells; at the late stage of infection (days 14 and 21), consistent with increased GATA3 mRNA expression and CD4+GATA3+ cells, IL-4 and IL-13 levels significantly increased; IL-17A level, Foxp3 mRNA expression, CD4+ROR-γt+ cells and CD4+FOXP3+ cells remained at higher levels throughout the course of the infection. Small-airway function showed a decline from day 3 to day 21; large airway function showed a decline on day 14 and 21. Overall, P. aeruginosa infection contributed to the progression of COPD. During the infection, an early Th1-related inflammation gradually shifted to a later Th2-related inflammation, and small-airway function decline occurred earlier than that of large-airway function. On the basis of infection control, the appropriate use of glucocorticoid might slow disease progression by mitigating the enhanced Th2-related inflammation, and small airways could be also an important treatment target in P. aeruginosa -infected COPD patients.
Insights
Pseudomonas aeruginosa infection worsens COPD progression by altering lung structure and function. Early Th1 inflammation shifts to Th2, suggesting glucocorticoids and small airway focus may aid treatment.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Immunology
Background:
- Pseudomonas aeruginosa (P. aeruginosa) is frequently found in COPD patients.
- Its exact role in COPD progression and inflammation modulation is not fully understood.
Purpose of the Study:
- To investigate the impact of P. aeruginosa infection on COPD progression in a mouse model.
- To analyze dynamic changes in lung structure, inflammatory microenvironment, and lung function.
Main Methods:
- Established COPD mouse models infected with P. aeruginosa.
- Monitored mucus secretion, airway remodeling, emphysema, inflammatory cytokine/cell profiles (Th1, Th2, Th17, Treg), and lung function over time.
Main Results:
- P. aeruginosa infection increased mucus, caused airway remodeling and emphysema.
- Early Th1-biased inflammation (IFN-γ, IL-5, T-bet) shifted to late Th2 (IL-4, IL-13, GATA3).
- Th17 and Treg markers remained elevated; small airway function declined earlier than large airway function.
Conclusions:
- P. aeruginosa infection exacerbates COPD, characterized by a shift from Th1 to Th2 inflammation.
- Targeting Th2 inflammation with glucocorticoids and focusing on small airways may be beneficial for P. aeruginosa-infected COPD patients.
