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Pneumocystis Colonization Is Associated with Enhanced Pulmonary Remodeling and Activation of Redox-Responsive
Andrea Méndez1,2, Krishna Coronado3, Diego A Rojas3
1Escuela de Kinesiología, Facultad de Salud y CIencias Sociales, Campus Providencia, Sede Santiago, Universidad de Las Américas, Santiago 7500975, Chile.
Abstract:
Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent inflammation and structural alterations in the lung triggered mainly by oxidative stress. Colonization by the opportunistic fungus Pneumocystis has been associated with worse clinical outcomes in COPD, yet its role in airway remodeling remains unclear. To this end, an elastase-induced COPD model was established, followed by colonization with Pneumocystis. Lung tissue was analyzed histologically and molecularly to assess epithelial thickness, alveolar morphometric parameters (mean linear intercept [MLI], D0, D1, D2), inflammation, collagen deposition, and the expression of remodeling and oxidative stress markers. Emphysematous damage parameters MLI, D0, D1, and D2 were markedly elevated in co-exposed animals, indicating enhanced alveolar enlargement. Animals with COPD and Pneumocystis colonization showed a significant increase in airway inflammation compared with control, COPD, and Pneumocystis groups. Airway epithelial thickness, mucus metaplasia, and collagen deposition exhibited a summative increase in the COPD/Pneumocystis group. Redox-responsive markers, such as superoxide dismutase (SOD) and catalase, were upregulated. Moreover, protein and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (Hmox1) were significantly increased, with the strongest activation observed in co-exposed animals. Integrative correlation analysis showed that Pneumocystis burden positively correlated with lung damage, inflammation, and epithelial remodeling. These structural alterations were accompanied by coordinated activation of the antioxidant pathway Nrf2. Taken together, Pneumocystis colonization is associated with enhanced pulmonary remodeling and modulation of antioxidant signaling in experimental COPD, promoting structural and molecular changes that may contribute to disease progression. These findings suggest that Pneumocystis acts as an amplifying factor in COPD-associated lung damage.
Insights
Pneumocystis fungal colonization worsens Chronic Obstructive Pulmonary Disease (COPD) lung damage and inflammation. This fungal co-infection amplifies airway remodeling and activates antioxidant pathways in experimental COPD models.
Area of Science:
- Pulmonary Medicine
- Medical Mycology
- Molecular Biology
Background:
- Chronic Obstructive Pulmonary Disease (COPD) involves lung inflammation and structural changes, often linked to oxidative stress.
- Pneumocystis fungal colonization is observed in COPD patients and associated with poorer outcomes, but its role in airway remodeling is not fully understood.
Purpose of the Study:
- To investigate the impact of Pneumocystis colonization on airway remodeling and oxidative stress in an experimental COPD model.
- To elucidate the molecular mechanisms underlying the interaction between Pneumocystis and COPD lung pathology.
Main Methods:
- An elastase-induced COPD model in rodents was established and subsequently colonized with Pneumocystis.
- Lung tissues were analyzed using histological and molecular techniques to assess inflammation, epithelial changes, alveolar damage, and oxidative stress markers.
- Expression levels of antioxidant pathway markers, including Nrf2 and Hmox1, were quantified.
Main Results:
- Pneumocystis co-exposure significantly exacerbated emphysematous damage, airway inflammation, epithelial thickness, and collagen deposition compared to COPD or Pneumocystis alone.
- Antioxidant markers like SOD and catalase were upregulated, alongside increased Nrf2 and Hmox1 expression, particularly in co-exposed animals.
- Pneumocystis burden positively correlated with lung damage, inflammation, and remodeling, indicating its role as an amplifying factor.
Conclusions:
- Pneumocystis colonization exacerbates pulmonary remodeling and modulates antioxidant signaling in experimental COPD.
- These structural and molecular changes driven by Pneumocystis may contribute to COPD progression.
- Pneumocystis acts as an amplifying factor in COPD-associated lung damage, highlighting potential therapeutic targets.
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