References of "Sabatel, Catherine"
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See detailCaractérisation ontogénique, phénotypique et fonctionnelle des macrophages interstitiels pulmonaires après exposition à des composés bactériens
Sabatel, Catherine ULiege

Doctoral thesis (2017)

Respiratory mucosal surfaces are continuously exposed to harmless antigens and immunostimulatory molecules of microbial origin. According to the « self/non self » and « danger » theories, this should ... [more ▼]

Respiratory mucosal surfaces are continuously exposed to harmless antigens and immunostimulatory molecules of microbial origin. According to the « self/non self » and « danger » theories, this should normally result in the developpment of unwanted immune responses towards these inhaled antigens such as Th2-mediated allergic responses. This is however not the case in most people. The hygiene hypothesis postulates that living in an environment rich in microbial components paradoxically protects from airway allergy, implying the existence in the lung of suppressive mechanisms triggered by these immunogenic signals. In this study, we showed that synthetic bacterial DNA rich in unmethylated CpG motifs (CpG) has the unique ability to significantly increase the population of lung interstitial regulatory macrophages (IM) from CCR2-independent monocytes residing in the lung or mobilized from the spleen. Moreover these CpG-induced IM demonstrated a hypersuppressive profile as they produced more IL-10 than their steady state counterparts. Using mice models of airway allergy we showed that the transfert of IM isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. This IM-mediated protection was dependant from IL-10 as CpG-induced Il10-/- IM had no protective effect. The expansion of pulmonary regulatory IM from CCR2-independent pulmonary and splenic monocytes upon CpG exposure could be a possible mechanism by which exposure to an environment rich in microbial products protects against asthma. [less ▲]

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See detailRelease of Neutrophils Extracellular Traps as a main trigger for asthma onset
Radermecker, Coraline ULiege; Sabatel, Catherine ULiege; Toussaint, Marie et al

Poster (2017, June 20)

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 37 (4 ULiège)
See detailRelease of Neutrophils Extracellular Traps as a main trigger for asthma onset
Radermecker, Coraline ULiege; Sabatel, Catherine ULiege; Toussaint, Marie et al

Conference (2017, January 24)

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 49 (0 ULiège)
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See detailA gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes.
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Xiao, Xue ULiege et al

in Nature Immunology (2017)

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we ... [more ▼]

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the TH2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection. [less ▲]

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See detailExposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.
Sabatel, Catherine ULiege; Radermecker, Coraline ULiege; Fievez, Laurence ULiege et al

in Immunity (2017), 46(3), 457-473

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major ... [more ▼]

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. Using a mouse model of allergic airway inflammation, we found that adoptive transfer of IMs isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. IM-mediated protection was dependent on IL-10, given that Il10-/- CpG-induced IMs lacked regulatory effects. Thus, the expansion of regulatory lung IMs upon exposure to CpG might underlie the reduced risk of asthma development associated with a microbe-rich environment. [less ▲]

Detailed reference viewed: 109 (26 ULiège)
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See detailCpG-DNA expand immunosuppressive interstitial macrophages from Ly6c+ local precursors
Sabatel, Catherine ULiege; Radermecker, Coraline ULiege; Fievez, Laurence ULiege et al

in Proceeding of Cell Symposia: 100 years of phagocytes (2016, September)

Detailed reference viewed: 29 (8 ULiège)
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See detailA gammaherpesvirus infection protects from allergic asthma development
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Xiao, X. et al

Conference (2015, December)

Detailed reference viewed: 8 (0 ULiège)
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See detailA gammaherpes
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Xiao, X. et al

Conference (2015, November)

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See detailA gammaherpesvirus infection protects from allergic asthma development
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Xiao, X. et al

Conference (2015, October)

Detailed reference viewed: 9 (0 ULiège)
Peer Reviewed
See detailA gammaherpesvirus infection protects against allergic asthma.
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Sabatel, Catherine ULiege et al

Poster (2014, December 12)

The “hygiene hypothesis” proposes that the augmentation of allergic diseases in developed countries could be linked to a reduced exposure to infections during childhood. Surprisingly, the potential ... [more ▼]

The “hygiene hypothesis” proposes that the augmentation of allergic diseases in developed countries could be linked to a reduced exposure to infections during childhood. Surprisingly, the potential protective role of herpesvirus infections against allergy development has never been addressed directly. In this study, we used the Murid herpesvirus 4 (MuHV-4) to study the impact of a persistent gammaherpesvirus infection on the development of House Dust Mites (HDM)-induced allergic asthma. Our results revealed that MuHV-4 infection affects both the sensitization and the challenging phases of HDM-induced airway allergy. In particular, we highlighted that MuHV-4 infection strongly impacts the lung innate immune response. Indeed, while the dendritic cells remained competent to uptake antigens and to migrate to the draining lymph nodes, MuHV-4 infection impaired their ability to trigger HDM sensitization. In the future, these results could allow us to develop strategies to prevent the development of TH2-skewed responses against respiratory allergens. [less ▲]

Detailed reference viewed: 54 (18 ULiège)