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

Margherita Bertuzzi, Gareth Howell, Darren Thomson, Rachael Fortune-Grant, Anna Möslinger, Patrick Dancer, Norman Van Rhijn, Natasha Motsi, Alice Codling, Elaine Bignell

Research output: Contribution to journalArticlepeer-review

Abstract

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 suggest that interactions with alveolar epithelial cells (AECs) are frequent; thus, we hypothesised 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 internalised and killed by AECs during whole animal infection. Moreover, comparative analysis of primary human AECs from healthy and 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.
Original languageEnglish
JournaliScience
Publication statusAccepted/In press - 5 May 2024

Keywords

  • Aspergillus fumigatus
  • lung epithelium
  • alveolar epithelial cells
  • antimicrobial epithelial activities
  • spore uptake

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