A novel mouse model of chronic <i>Pseudomonas aeruginosa</i> infection inducing bronchiectasis‐like phenotype

BACKGROUND: Given the need to translate basic research into human therapies, the development and refinement of clinically relevant animal models for bronchiectasis are critically important. To date, there are no well-established animal models for bronchiectasis. Thus, our aim was to develop a novel animal model that accurately recapitulates bronchiectasis-like pathologies. METHODS: To address this question, clinical strains of chronic Pseudomonas aeruginosa (CPA) were embedded in agar beads in vitro; then CPA-loaded agar beads and papain were repeatedly instilled intratracheally in female C57BL/6 J mice. Experimental assessments included micro-computed tomography (micro-CT) imaging, histological analysis, immune cell infiltration, cytokines, and lung function parameter measurements to evaluate structural damage, immune responses, and lung function impairments in the mouse model. RESULTS: In this mouse model, we observed that lung micro-CT imaging revealed significant bronchiectasis, with visible airways in the periphery, cylindrical airway expansion, and an airway-to-artery ratio > 1. Histopathology highlighted immune cell infiltration around the trachea, including lymphocytes, neutrophils, and monocytes, along with Periodic acid-Schiff staining-positive hypermucinous secretion. Compared to controls, the bronchiectasis group exhibited elevated pro-inflammatory cytokines in bronchoalveolar lavage fluid and worse lung function. CONCLUSION: Our study presented a novel mouse model that better replicated the bronchiectasis-like phenotype than the CPA airway infection model, showing the advantages of the "CPA-loaded agar beads and papain"-driven approach in optimizing the disease models. The model mimicked the progression of bronchiectasis closely and could be used for studies on disease pathogenesis as well as the evaluation of novel therapies in the near future.