EphA2-Dependent Internalization of A. fumigatus Conidia in A549 Lung Cells Is Modulated by DHN-Melanin
| Autor: | Keizer, Esther M., Wösten, Han A. B., de Cock, Hans, Sub Molecular Microbiology, Molecular Microbiology |
|---|---|
| Přispěvatelé: | Molecular Microbiology, Sub Molecular Microbiology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
medicine.drug_class media_common.quotation_subject education lcsh:QR1-502 EphA2 Monoclonal antibody Microbiology A. fumigatus lcsh:Microbiology Aspergillus fumigatus 03 medical and health sciences medicine Ephrin aspergillosis Internalization Receptor Original Research 030304 developmental biology media_common A549 cell 0303 health sciences biology 030306 microbiology Chemistry Kinase biology.organism_classification lung epithelial cells Molecular biology internalization DHN-melanin biology.protein Antibody |
| Zdroj: | Frontiers in Microbiology, 11, 1. Frontiers Media S.A. Frontiers in Microbiology, Vol 11 (2020) Frontiers in Microbiology |
| ISSN: | 1664-302X |
| Popis: | Dectin-1 and ephrin type-A receptor 2 (EphA2) receptors recognize beta-glucan present in the fungal cell wall. Inhibition of Dectin-1 with the monoclonal 2a11 antibody was shown to reduce internalization of conidia of the human pathogenAspergillus fumigatusinto epithelial cells. In this study, we investigated the role of the EphA2 receptor present on A549 epithelial type II lung cells in the interaction withA. fumigatusconidia. We assessed whether EphA2 is involved in association and internalization of conidia by receptor inhibition by an antibody or by using the kinase inhibitor dasatinib. A 50% reduction of internalization of conidia was observed when this receptor was blocked with either the EphA2-specific monoclonal antibody or dasatinib, which was similar when Dectin-1 was inhibited with the 2a11 monoclonal antibody. Inhibition of both receptors reduced the internalization to 40%. EphA2 inhibition was also assessed in a hydrophobin deletion strain (Delta rodA) that exposes more beta-glucan and a dihydroxynaphthalene (DHN)-melanin deletion strain (Delta pksP) that exposes more glucosamine and glycoproteins. The Delta rodAstrain behaved similar to the wild-type strain with or without EphA2 inhibition. In contrast, the Delta pksPmutant showed an increase in association to the A549 cells and a decrease in internalization. Internalization was not further decreased by EphA2 inhibition. Taken together, the presence of DHN-melanin in the spore cell wall results in an EphA2-dependent internalization of conidia ofA. fumigatusinto A549 cells. |
| Databáze: | OpenAIRE |
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