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Poster (Scientific congresses and symposiums)
Release of Neutrophils Extracellular Traps as a main trigger for asthma onset
Radermecker, Coraline; Sabatel, Catherine; Toussaint, Marie et al.
2017European Academy of Allergy and Clinical Immunology
 

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Keywords :
Neutrophils; Asthma; Neutrophils Extracellular traps
Abstract :
[en] Allergic asthma is an important Th2 associated immunopathology. Even if the pathology of the disease is well described, its etiology is still largely unknown. Nevertheless, some environmental factors like viral infections and exposition to low doses of lipopolysaccharide (LPS) strongly increase the risk of disease inception. Interestingly, these two particular risk factors both induce a strong recruitment of neutrophils into the lung. Recently, scientists highlighted the ability of neutrophils to form neutrophils extracellular traps (NETs) composed of a network of extracellular DNA associated to anti-microbial peptides. NETs release (or NETosis) is an important component in organism defence against pathogen invasion but has also been identified as initiator of pathophysiological conditions like erythematous systemic lupus, gout and diabetes. In this study, we investigated the role of NETs as potential asthma inducers in specific pro-Th2 environmental risk factors like respiratory viral infections and low LPS doses exposures (also known as hygiene hypothesis). First, we assessed the correlation between respiratory viral infection or low LPS exposure and NETosis using western blot and confocal microscopy analysis. An influenza A infection induced a strong NETs release between day three and seven after viral inoculation whereas exposition to low (100 ng LPS) but not to high (10 µg LPS) LPS doses also promoted NETosis within 24 hours following the exposition. Then we developed two mouse models, a virus-induced asthma model and a model of asthma promoted by exposition to low LPS doses. In these models, only previously infected mice or mice exposed to low LPS doses displayed all the characteristics of allergic asthma following sensitization and challenge to house dust mite (HDM). The role of NETs in asthma onset was then demonstrated using three NETosis inhibitors (DNAse, Cl-amidine and inhibitor of neutrophil elastase) in our models as infected or low LPS doses exposed mice exhibited strong decreased of all key asthma features when treated with NETs inhibitors compared to non-treated mice. Finally, to address how NETs could lead to a TH2 immune response, we analysed by flow cytometry the distinct subpopulations of lung dendritic cells (DCs) in our two mice models. We observed, during the NETs release phase, a recruitment of monocytic derived DCs (moDCs). In conclusion, we have demonstrated an unexpected role for NETs in asthma onset by recruiting lung moDCs.
Disciplines :
Immunology & infectious disease
Author, co-author :
Radermecker, Coraline ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Sabatel, Catherine ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Toussaint, Marie;  Université de Liège - ULiège > Immunologie Cellulaire et Moléculaire
Johnston, Sebastian;  Imperial College London > Airway Disease Infection Section > National Lung and Heart Disease Institute
Bureau, Fabrice ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Marichal, Thomas  ;  Université de Liège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Language :
English
Title :
Release of Neutrophils Extracellular Traps as a main trigger for asthma onset
Publication date :
20 June 2017
Number of pages :
Poster
Event name :
European Academy of Allergy and Clinical Immunology
Event place :
Finland
Event date :
17 au 21 juin 2017
Audience :
International
Available on ORBi :
since 11 July 2017

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