
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.09.612147
preprint
1
Article
Single-cell analysis of human airway epithelium identifies cell type-specific responses to Aspergillus and Coccidioides
Harding Alfred T.
Crossen Arianne J.
Reedy Jennifer L.
Basham Kyle J.
Hepworth Olivia W.
Zhang Yanting
Shah Viral S.
Harding Hannah Brown
Surve Manalee V.
Simaku Patricia
Kwaku Geneva N.
Jensen Kristine Nolling
Otto Yohana
Ward Rebecca A. http://orcid.org/0000-0001-6752-5600

Thompson George R.
Klein Bruce S.
Rajagopal Jayaraj
Sen Pritha
Haber Adam L.
Vyas Jatin M. http://orcid.org/0000-0002-9985-9565

13 9 2024
2024.09.09.612147https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.09.612147
nihpp-2024.09.09.612147.pdf
Abstract

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 in vitro and investigate cellular responses to two diverse, clinically significant fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii . 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 A. fumigatus and C. posadasii 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 A. fumigatus or C. posadasii , providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways.

Importance

Fungal infections in the lungs are dreaded complications for those with compromised immune systems and have limited treatment strategies available. These options are restricted further by the increased prevalence of treatment-resistant fungi. Many studies focus on how our immune systems respond to these pathogens, yet airway epithelial cells remain an understudied component of fungal infections in the lungs. Here, the authors provide a transcriptional analysis of primary human airway epithelial cells stimulated by two distinct fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii . These data will enable further mechanistic studies of the contribution of the airway epithelium to initial host responses and represent a powerful new resource for investigators.
==== Body
pmc
