Cargando…

Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model

Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. Aspergillus (A.) fumigatus, the most prevalent pathogenic fungus, affects both upper and lower respiratory tracts of immunocompromised hosts. Sever...

Descripción completa

Detalles Bibliográficos
Autores principales: Luvanda, Maureen K., Posch, Wilfried, Noureen, Asma, Lafon, Eliott, Zaderer, Viktoria, Lass-Flörl, Cornelia, Wilflingseder, Doris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003030/
https://www.ncbi.nlm.nih.gov/pubmed/33803702
http://dx.doi.org/10.3390/jof7030221
_version_ 1783671593606578176
author Luvanda, Maureen K.
Posch, Wilfried
Noureen, Asma
Lafon, Eliott
Zaderer, Viktoria
Lass-Flörl, Cornelia
Wilflingseder, Doris
author_facet Luvanda, Maureen K.
Posch, Wilfried
Noureen, Asma
Lafon, Eliott
Zaderer, Viktoria
Lass-Flörl, Cornelia
Wilflingseder, Doris
author_sort Luvanda, Maureen K.
collection PubMed
description Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. Aspergillus (A.) fumigatus, the most prevalent pathogenic fungus, affects both upper and lower respiratory tracts of immunocompromised hosts. Several reports implicate corticosteroids as a major risk factor due to their anti-inflammatory and immunosuppressive effects, which are exacerbated by long-term treatment regimens. Here we demonstrate for the first time the influence of dexamethasone when it comes to germination and hyphae formation of A. fumigatus in the presence of macrophages within a highly differentiated air–liquid interphase (ALI) epithelial/immune lung model. We illustrate suppressed mucus production within the highly differentiated 3D respiratory model as well as significantly decreased cilia beat frequencies by dexamethasone treatment. This goes along with corticosteroid-mediated macrophage M2 polarization within the epithelial/immune microenvironment. Therefore, we here showed that corticosteroids promote enhanced fungal growth and invasion A. fumigatus by creating a suppressive environment affecting both epithelial as well as immune cells.
format Online
Article
Text
id pubmed-8003030
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80030302021-03-28 Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model Luvanda, Maureen K. Posch, Wilfried Noureen, Asma Lafon, Eliott Zaderer, Viktoria Lass-Flörl, Cornelia Wilflingseder, Doris J Fungi (Basel) Article Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. Aspergillus (A.) fumigatus, the most prevalent pathogenic fungus, affects both upper and lower respiratory tracts of immunocompromised hosts. Several reports implicate corticosteroids as a major risk factor due to their anti-inflammatory and immunosuppressive effects, which are exacerbated by long-term treatment regimens. Here we demonstrate for the first time the influence of dexamethasone when it comes to germination and hyphae formation of A. fumigatus in the presence of macrophages within a highly differentiated air–liquid interphase (ALI) epithelial/immune lung model. We illustrate suppressed mucus production within the highly differentiated 3D respiratory model as well as significantly decreased cilia beat frequencies by dexamethasone treatment. This goes along with corticosteroid-mediated macrophage M2 polarization within the epithelial/immune microenvironment. Therefore, we here showed that corticosteroids promote enhanced fungal growth and invasion A. fumigatus by creating a suppressive environment affecting both epithelial as well as immune cells. MDPI 2021-03-18 /pmc/articles/PMC8003030/ /pubmed/33803702 http://dx.doi.org/10.3390/jof7030221 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Luvanda, Maureen K.
Posch, Wilfried
Noureen, Asma
Lafon, Eliott
Zaderer, Viktoria
Lass-Flörl, Cornelia
Wilflingseder, Doris
Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title_full Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title_fullStr Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title_full_unstemmed Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title_short Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model
title_sort dexamethasone creates a suppressive microenvironment and promotes aspergillus fumigatus invasion in a human 3d epithelial/immune respiratory model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003030/
https://www.ncbi.nlm.nih.gov/pubmed/33803702
http://dx.doi.org/10.3390/jof7030221
work_keys_str_mv AT luvandamaureenk dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT poschwilfried dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT noureenasma dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT lafoneliott dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT zadererviktoria dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT lassflorlcornelia dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel
AT wilflingsederdoris dexamethasonecreatesasuppressivemicroenvironmentandpromotesaspergillusfumigatusinvasioninahuman3depithelialimmunerespiratorymodel