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Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells

BACKGROUND: Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. METHODS: This in vitro study on human pDC isola...

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Autores principales: Zurmühl, Noelle, Schmitt, Anna, Formentini, Ulrike, Weiss, Johannes, Appel, Heike, Debatin, Klaus-Michael, Fabricius, Dorit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597288/
https://www.ncbi.nlm.nih.gov/pubmed/34789269
http://dx.doi.org/10.1186/s12948-021-00163-8
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author Zurmühl, Noelle
Schmitt, Anna
Formentini, Ulrike
Weiss, Johannes
Appel, Heike
Debatin, Klaus-Michael
Fabricius, Dorit
author_facet Zurmühl, Noelle
Schmitt, Anna
Formentini, Ulrike
Weiss, Johannes
Appel, Heike
Debatin, Klaus-Michael
Fabricius, Dorit
author_sort Zurmühl, Noelle
collection PubMed
description BACKGROUND: Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. METHODS: This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. RESULTS: We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. CONCLUSIONS: To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12948-021-00163-8.
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spelling pubmed-85972882021-11-17 Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells Zurmühl, Noelle Schmitt, Anna Formentini, Ulrike Weiss, Johannes Appel, Heike Debatin, Klaus-Michael Fabricius, Dorit Clin Mol Allergy Research BACKGROUND: Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. METHODS: This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. RESULTS: We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. CONCLUSIONS: To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12948-021-00163-8. BioMed Central 2021-11-17 /pmc/articles/PMC8597288/ /pubmed/34789269 http://dx.doi.org/10.1186/s12948-021-00163-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zurmühl, Noelle
Schmitt, Anna
Formentini, Ulrike
Weiss, Johannes
Appel, Heike
Debatin, Klaus-Michael
Fabricius, Dorit
Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title_full Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title_fullStr Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title_full_unstemmed Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title_short Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
title_sort differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597288/
https://www.ncbi.nlm.nih.gov/pubmed/34789269
http://dx.doi.org/10.1186/s12948-021-00163-8
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