Aspergillus fumigatus cell wall promotes apical airway epithelial recruitment of human neutrophils.
Infect Immun. 2019 Nov 25;:
Authors: Feldman MB, Dutko RA, Wood M, Ward RA, Leung HM, Snow RF, de La Flor DJ, Yonker LM, Reedy JL, Tearney GJ, Mou H, Hurley BP, Vyas JM
Aspergillus fumigatus is a ubiquitous fungal pathogen capable of causing multiple pulmonary diseases including invasive aspergillosis, chronic necrotizing aspergillosis, fungal colonization, and allergic bronchopulmonary aspergillosis. Intact mucocilliary barrier function and early airway neutrophil responses are critical for clearing fungal conidia from the host airways prior to establishing disease. Following inhalation, Aspergillus conidia deposit in the small airways where they are likely to make their initial host encounter with epithelial cells. Challenges in airway infection models have limited the ability to explore early steps in the interactions between A. fumigatus and human airway epithelium. Here, we use inverted air-liquid interface cultures to demonstrate that human airway epithelium responds to apical stimulation by A. fumigatus to promote transepithelial migration of neutrophils from the basolateral membrane surface to the apical “airway” surface. Promoting epithelial transmigration with Aspergillus required prolonged exposure with live resting conidia. Swollen conidia did not expedite epithelial transmigration. Using A. fumigatus strains containing genetic deletions of cell wall components, we identified that deletion of the hydrophobic rodlet layer or DHN-melanin in the conidial cell wall amplified epithelial transmigration of neutrophils, using primary human airway epithelium. Ultimately, we show that an as-yet unidentified non-secreted cell wall protein is required to promote early epithelial transmigration of human neutrophils into the airspace in response to A. fumigatus Together, these data provide critical insight into initial epithelial host response to Aspergillus.
PMID: 31767773 [PubMed – as supplied by publisher]