Ó³»­´«Ã½

Respiratory fungal infections pose a significant threat to human health. Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment and investigate cellular responses to two diverse, clinically significant fungal pathogens, and . To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with and triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either or , providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways.