Tracking the response to Pseudomonas aeruginosa infection in ozone-induced chronic obstructive pulmonary disease mouse models.

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.

• Authors: Lei Han, Yuning Huang, Qiang Fu, Yishu Xue, Fengming Ding, Min Zhang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 150 Pg. 112980 (Jun 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 35453008 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Forkhead Transcription Factors
• RNA, Messenger
• Ozone

Topics

• Animals
• Forkhead Transcription Factors (metabolism)
• Humans
• Inflammation
• Lung (metabolism)
• Mice
• Ozone
• Pseudomonas Infections (metabolism)
• Pseudomonas aeruginosa
• Pulmonary Disease, Chronic Obstructive
• RNA, Messenger