Animal models of fungus-related allergic airway disease: exposures, readouts, mechanisms, and translational gaps

Fungal sensitization is a major risk factor for severe asthma and related airway diseases, spanning presentations from simple sensitization to allergic bronchopulmonary aspergillosis (ABPA). To capture this spectrum, the concept of allergic fungal airway disease (AFAD) has been proposed. Animal models have been central to uncovering how fungi drive airway inflammation. Extract-based models are simple and reproducible and highlight epithelial alarm signaling and type 2 immunity, although they do not reflect chronic infection. Spore-based models using Aspergillus fumigatus or Alternaria alternata more closely mimic human disease, producing mixed eosinophilic and neutrophilic inflammation, airway hyperreactivity, and mucus plugging. Advances using clinical isolates, gene-edited fungal strains, and combined exposure systems (for example, cigarette smoke plus spores) have further improved relevance by linking fungal virulence and host factors to disease severity. This review summarizes available models, their strengths and limitations, and their utility in elucidating AFAD pathogenesis and informing therapy.