ULK1 mediated autophagy in airway cells during Aspergillus infection

Aspergillus fumigatus is a major airborne fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. This study aims to elucidate the autophagic mechanisms activated following the internalization of A. fumigatus conidia in human bronchial epithelial cells.

Specifically, we investigated the role of ULK1 and the autophagic processes in Beas2B cells upon A. fumigatus conidia internalization. The Beas2B cell line was used to assess the protein expression of ULK1, phosphorylated ULK1, and LC3-I/II via Western blotting. Autophagosome structures were examined using transmission electron microscopy. Gene silencing of ULK1 using siRNA and pharmacological inhibition with SBI-0206965 were performed. Secreted inflammatory cytokines were quantified using specific immunoassays.

A. fumigatus conidia induced a time- and dose-dependent conversion of LC3-I to LC3-II, indicating autophagic activation resembling LC3-associated phagocytosis (LAP). ULK1 expression significantly increased post-infection, whereas genetic silencing of ULK1 reduced LC3-II conversion. Notably, common fungal polysaccharides and Dectin-1 did not influence this process, but the loss of complement receptor 3 (CR3) elevated both basal and conidia-induced autophagy, correlating with increased AMPK expression.

This study reveals a novel ULK1-dependent autophagic response similar to LAP during A. fumigatus internalization, highlighting potential therapeutic targets for managing invasive aspergillosis in immunocompromised patients.