Epithelial uptake leads to fungal killing in vivo and is aberrant in COPD-derived epithelial cells

Autor: Margherita Bertuzzi, Gareth J. Howell, Darren D. Thomson, Rachael Fortune-Grant, Anna Möslinger, Patrick Dancer, Norman Van Rhijn, Natasha Motsi, Alice Codling, Elaine M. Bignell
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 109939- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109939
Popis: Summary: Hundreds of spores of Aspergillus fumigatus (Af) are inhaled daily by human beings, representing a constant, possibly fatal, threat to respiratory health. The small size of Af spores suggests that interactions with alveolar epithelial cells (AECs) are frequent; thus, we hypothesized that spore uptake by AECs is important for driving fungal killing and susceptibility to Aspergillus-related disease. Using single-cell approaches to measure spore uptake and its outcomes in vivo, we demonstrate that Af spores are internalized and killed by AECs during whole-animal infection. Moreover, comparative analysis of primary human AECs from healthy and chronic obstructive pulmonary disease (COPD) donors revealed significant alterations in the uptake and killing of spores in COPD-derived AECs. We conclude that AECs contribute to the killing of Af spores and that dysregulation of curative AEC responses in COPD may represent a driver of Aspergillus-related diseases.
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