Eosinophils capture viruses, a capacity that is defective in asthma.
Animals
Antigens, CD
/ metabolism
Antigens, Differentiation, T-Lymphocyte
/ metabolism
Asthma
/ diagnosis
Disease Models, Animal
Eosinophils
/ metabolism
Humans
Influenza A virus
/ physiology
Lectins, C-Type
/ metabolism
Lung
/ immunology
Mice
Mice, Transgenic
Respiratory Function Tests
Virus Diseases
/ complications
CD69
RSV
exacerbation
influenza
rhinovirus_16
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
18
10
2018
revised:
29
01
2019
accepted:
26
02
2019
pubmed:
2
4
2019
medline:
20
8
2020
entrez:
2
4
2019
Statut:
ppublish
Résumé
Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular antiviral activity by eosinophils. To follow eosinophil-virus interaction, respiratory syncytial virus (RSV) and influenza virus were labeled with a fluorescent lipophilic dye (DiD). Interactions with eosinophils were visualized by confocal microscopy, electron microscopy, and flow cytometry. Eosinophil activation was assessed by both flow cytometry and ELISA. In a separate study, eosinophils were depleted in asthma patients using anti-IL-5 (mepolizumab), followed by a challenge with rhinovirus-16 (RV16). DiD-RSV and DiD-influenza rapidly adhered to human eosinophils and were internalized and inactivated (95% in ≤ 2 hours) as reflected by a reduced replication in epithelial cells. The capacity of eosinophils to capture virus was reduced up to 75% with increasing severity of asthma. Eosinophils were activated by virus in vitro and in vivo. In vivo this correlated with virus-induced loss of asthma control. This previously unrecognized and in asthma attenuated antiviral property provides a new perspective to eosinophils in asthma. This is indicative of an imbalance between protective and cytotoxic properties by eosinophils that may underlie asthma exacerbations.
Sections du résumé
BACKGROUND
Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular antiviral activity by eosinophils.
METHODS
To follow eosinophil-virus interaction, respiratory syncytial virus (RSV) and influenza virus were labeled with a fluorescent lipophilic dye (DiD). Interactions with eosinophils were visualized by confocal microscopy, electron microscopy, and flow cytometry. Eosinophil activation was assessed by both flow cytometry and ELISA. In a separate study, eosinophils were depleted in asthma patients using anti-IL-5 (mepolizumab), followed by a challenge with rhinovirus-16 (RV16).
RESULTS
DiD-RSV and DiD-influenza rapidly adhered to human eosinophils and were internalized and inactivated (95% in ≤ 2 hours) as reflected by a reduced replication in epithelial cells. The capacity of eosinophils to capture virus was reduced up to 75% with increasing severity of asthma. Eosinophils were activated by virus in vitro and in vivo. In vivo this correlated with virus-induced loss of asthma control.
CONCLUSIONS
This previously unrecognized and in asthma attenuated antiviral property provides a new perspective to eosinophils in asthma. This is indicative of an imbalance between protective and cytotoxic properties by eosinophils that may underlie asthma exacerbations.
Identifiants
pubmed: 30934128
doi: 10.1111/all.13802
pmc: PMC6852198
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, T-Lymphocyte
0
CD69 antigen
0
Lectins, C-Type
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1898-1909Subventions
Organisme : Netherlands Asthma Foundation
Pays : International
Organisme : GSK
ID : CRT 114696
Pays : International
Informations de copyright
© 2019 The Authors. Allergy Published by John Wiley & Sons Ltd.
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