Phagocytosis of Aspergillus fumigatus by Human Bronchial Epithelial Cells Is Mediated by the Arp2/3 Complex and WIPF2

Frontiers in Cellular and Infection Microbiology
Luka CulibrkScott J Tebbutt

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen capable of causing severe infection in humans. One of the limitations in our understanding of how A. fumigatus causes infection concerns the initial stages of infection, notably the initial interaction between inhaled spores or conidia and the human airway. Using publicly-available datasets, we identified the Arp2/3 complex and the WAS-Interacting Protein Family Member 2 WIPF2 as being potentially responsible for internalization of conidia by airway epithelial cells. Using a cell culture model, we demonstrate that RNAi-mediated knockdown of WIPF2 significantly reduces internalization of conidia into airway epithelial cells. Furthermore, we demonstrate that inhibition of Arp2/3 by a small molecule inhibitor causes similar effects. Using super-resolution fluorescence microscopy, we demonstrate that WIPF2 is transiently localized to the site of bound conidia. Overall, we demonstrate the active role of the Arp2/3 complex and WIPF2 in mediating the internalization of A. fumigatus conidia into human airway epithelial cells.

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Citations

Nov 15, 2019·Clinical Microbiology Reviews·Jean-Paul Latgé, Georgios Chamilos
Jun 13, 2020·Frontiers in Immunology·Jeanne BigotChristophe Hennequin
Oct 31, 2020·Frontiers in Microbiology·Esther M KeizerHans de Cock
Jan 16, 2021·Cellular and Molecular Life Sciences : CMLS·Ashley B Strickland, Meiqing Shi

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Datasets Mentioned

BETA
SRA
SRR1565945
SRR1565946
SRR1565947
SRR1565948
SRR1565949
SRR1714495
SRR1714481
SRR1714483
SRR1714482

Methods Mentioned

BETA
RNA-seq
Confocal Microscopy
fluorescence microscopy

Software Mentioned

voom
mixOMICS
limma

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