Establishment of a novel murine model of allergic bronchopulmonary aspergillosis using an eosinophilic mutant mouse.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disorder caused by chronic exposure to Aspergillus fumigatus (Af). Existing mouse models do not fully capture the severity of ABPA. This study developed a novel murine model of ABPA using the spontaneously eosinophilic Yama mouse. Female Yama and BALB/c mice were sensitized and challenged with Asp f1, a major allergen derived from Af. Peripheral eosinophil counts, serum IgE levels, and histopathological changes in the lungs, including goblet cell hyperplasia, mucus plugging, collagen deposition, eosinophil cationic protein (ECP), and CD117/c-kit expression, were assessed. Cytokine and fibrosis-related gene mRNA expression of interleukin-4 (IL-4), IL-5, IL-6, IL-13, transforming growth factor-β (TGF-β), and Col1a1 was also measured. Compared to BALB/c mice, Asp f1-challenged Yama mice exhibited sustained eosinophilia, increased IgE, pronounced goblet cell hyperplasia with mucus plugging, collagen deposition, and elevated eosinophil cationic protein (ECP) expression. Yama mice also showed more significant peribronchial inflammation and pulmonary fibrosis. RT-PCR analysis demonstrated substantial increases in IL-4, IL-5, IL-6, IL-13, and Col1a1 transcripts, indicating a Th2-dominant immune profile and enhanced fibrotic activity. The minimal differences in TGF-β expression between Asp f1- and saline-treated mice indicate that fibrosis in Yama mice may proceed via a TGF-β-independent pathway. These findings establish the Yama mouse as a novel model for ABPA research, closely replicating the immunopathological features of severe human ABPA. This model provides a reliable platform to investigate eosinophil-driven lung fibrosis mechanisms and evaluate hypersensitivity responses contributing to human ABPA onset and progression.