References of "Bureau, Fabrice"
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See detailLoss of transfer RNA U34 modifying enzymes impairs hematopoietic stem and progenitor cell differentiation and function
Rosu, Adeline ULg; Bai, Qiang ULg; Ramery, Eve ULg et al

Poster (2017, February 03)

Hematopoietic stem and progenitor cells (HSPCs) require fine-tuned protein translation for their normal maintenance and function. Conserved modifications of the wobble uridine base (U34) in transfer RNAs ... [more ▼]

Hematopoietic stem and progenitor cells (HSPCs) require fine-tuned protein translation for their normal maintenance and function. Conserved modifications of the wobble uridine base (U34) in transfer RNAs catalyzed by the Elongator complex are required for optimal protein translation efficacy and fidelity, but their biological importance in mammalian stem and progenitor cells remains largely unexplored. Here, we studied the impact of loss of activity of the catalytic subunit Elp3 of Elongator on HSPC differentiation and function. Hematopoietic-cell-specific depletion of Elp3 in conditional knockout mice resulted in shortened lifespan associated with hematopoietic failure and lymphoma development. Elp3 deletion caused apoptosis of specific bone marrow multipotent progenitors and blocked differentiation of committed progenitors, resulting in blood and bone marrow pancytopenia. In contrast, Elp3-deficient hematopoietic stem cells (HSCs) expanded with age and did not exhaust throughout life, although they were defective in reconstituting hematopoiesis in competitive transplantation assays. Mechanistically, loss of Elp3 did not result in detectable alterations in global protein synthesis rates in any HSPC subset. Rather, Elp3-deficient HSPCs displayed enhanced activity of the stress integrator and apoptosis and cell cycle regulator p53. Thus, this study supports the notion that Elongator activity is required in distinct HSPC subsets to avoid aberrant p53 activation, which otherwise results in discrete loss of function phenotypes in HSCs and downstream progenitors. [less ▲]

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See detailHost DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.
Toussaint, Marie; Jackson, David J.; Swieboda, Dawid et al

in Nature Medicine (2017)

Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus ... [more ▼]

Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or by degrading NETs with DNase protects mice from type-2 immunopathology. Furthermore, the injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type-2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations. [less ▲]

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

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See detailLung resident eosinophils represent a distinct cell subset with homeostatic functions
Mesnil, Claire ULg; Raulier, Stéfanie ULg; Paulissen, Geneviève et al

Conference (2016, October 21)

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See detailCpG-DNA expand immunosuppressive interstitial macrophages from Ly6c+ local precursors
Sabatel, Catherine ULg; Radermecker, Coraline ULg; Fievez, Laurence ULg et al

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

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See detailAsthma inflammatory phenotypes show differential microRNA expression in sputum.
Maes, Tania; Cobos, Francisco Avila; SCHLEICH, FLorence ULg et al

in The Journal of allergy and clinical immunology (2016), 137(5), 1433-46

BACKGROUND: Asthma is classified according to severity and inflammatory phenotype and is likely to be distinguished by specific microRNA (miRNA) expression profiles. OBJECTIVE: We sought to associate ... [more ▼]

BACKGROUND: Asthma is classified according to severity and inflammatory phenotype and is likely to be distinguished by specific microRNA (miRNA) expression profiles. OBJECTIVE: We sought to associate miRNA expression in sputum supernatants with the inflammatory cell profile and disease severity in asthmatic patients. METHODS: We investigated miRNA expression in sputum supernatants of 10 healthy subjects, 17 patients with mild-to-moderate asthma, and 9 patients with severe asthma using high-throughput, stem-loop, reverse transcriptase quantitative real-time PCR miRNA expression profiling (screening cohort, n = 36). Differentially expressed miRNAs were validated in an independent cohort (n = 60; 10 healthy subjects and 50 asthmatic patients). Cellular miRNA origin was examined by using in situ hybridization and reverse transcriptase quantitative real-time PCR. The functional role of miRNAs was assessed by using in silico analysis and in vitro transfecting miRNA mimics in human bronchial epithelial cells. RESULTS: In 2 independent cohorts expression of miR-629-3p, miR-223-3p, and miR-142-3p was significantly upregulated in sputum of patients with severe asthma compared with that in healthy control subjects and was highest in patients with neutrophilic asthma. Expression of the 3 miRNAs was associated with sputum neutrophilia, and miR-223-3p and miR-142-3p expression was associated also with airway obstruction (FEV1/forced vital capacity). Expression of miR-629-3p was localized in the bronchial epithelium, whereas miR-223-3p and miR-142-3p were expressed in neutrophils, monocytes, and macrophages. Transfecting human bronchial epithelial cells with miR-629-3p mimic induced epithelial IL-8 mRNA and protein expression. IL-1beta and IL-8 protein levels were significantly increased in sputum of patients with severe asthma and were positively associated with sputum neutrophilia. CONCLUSIONS: Expression of miR-223-3p, miR-142-3p, and miR-629-3p is increased in sputum of patients with severe asthma and is linked to neutrophilic airway inflammation, suggesting that these miRNAs contribute to this asthma inflammatory phenotype. [less ▲]

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See detailLung-resident eosinophils represent a distinct regulatory eosinophil subset
Mesnil, Claire ULg; Raulier, Stéfanie ULg; Paulissen, G et al

in Journal of Clinical Investigation (2016), 126(9), 3275-3295

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the ... [more ▼]

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5–independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite–induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5–dependent peribronchial Siglec-FhiCD62L–CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. [less ▲]

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See detailGuanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis.
Marichal, Thomas ULg; Gaudenzio, Nicolas; El Abbas, Sophie ULg et al

in Journal of Clinical Investigation (2016), 126(12), 4497-4515

Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we ... [more ▼]

Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we have found that keratinocyte-specific deletion of the gene encoding RAB guanine nucleotide exchange factor 1 (RABGEF1, also known as RABEX-5) severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RABGEF1-deficient keratinocytes exhibited aberrant activation of the intrinsic IL-1R/MYD88/NF-kappaB signaling pathway and MYD88-dependent abnormalities in expression of structural proteins that contribute to skin barrier function. Moreover, ablation of MYD88 signaling in RABGEF1-deficient keratinocytes or deletion of Il1r1 restored skin homeostasis and prevented development of skin inflammation. We further demonstrated that epidermal RABGEF1 expression is reduced in skin lesions of humans diagnosed with either atopic dermatitis or allergic contact dermatitis as well as in an inducible mouse model of allergic dermatitis. Our findings reveal a key role for RABGEF1 in dampening keratinocyte-intrinsic MYD88 signaling and sustaining epidermal barrier function in mice, and suggest that dysregulation of RABGEF1 expression may contribute to epidermal barrier dysfunction in allergic skin disorders in mice and humans. Thus, RABGEF1-mediated regulation of IL-1R/MYD88 signaling might represent a potential therapeutic target. [less ▲]

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See detailA molecular approach for the rapid, selective and sensitive detection of Exophiala jeanselmei in environmental samples: development and performance assessment of a real-time PCR assay.
Libert, X.; Chasseur, C.; Packeu, A. et al

in Applied Microbiology and Biotechnology (2016), 100(3), 1377-1392

Exophiala jeanselmei is an opportunistic pathogenic black yeast growing in humid environments such as water reservoirs of air-conditioning systems. Because this fungal contaminant could be vaporized into ... [more ▼]

Exophiala jeanselmei is an opportunistic pathogenic black yeast growing in humid environments such as water reservoirs of air-conditioning systems. Because this fungal contaminant could be vaporized into the air and subsequently cause health problems, its monitoring is recommended. Currently, this monitoring is based on culture and microscopic identification which are complex, sometimes ambiguous and time-demanding, i.e., up to 21 days. Therefore, molecular, culture-independent methods could be more advantageous for the monitoring of E. jeanselmei. In this study, we developed a SYBR(R)green real-time PCR assay based on the internal transcribed spacer 2 from the 18S ribosomal DNA complex for the specific detection of E. jeanselmei. The selectivity (100 %), PCR efficiency (95.5 %), dynamic range and repeatability of this qPCR assay were subsequently evaluated. The limit of detection for this qPCR assay was determined to be 1 copy of genomic DNA of E. jeanselmei. Finally, water samples collected from cooling reservoirs were analyzed using this qPCR assay to deliver a proof of concept for the molecular detection of E. jeanselmei in environmental samples. The results obtained by molecular analysis were compared with those of classical methods (i.e., culture and microscopic identification) used in routine analysis and were 100 % matching. This comparison demonstrated that this SYBR(R)green qPCR assay can be used as a molecular alternative for monitoring and routine investigation of samples contaminated by E. jeanselmei, while eliminating the need for culturing and thereby considerably decreasing the required analysis time to 2 days. [less ▲]

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See detailEffect of a CpG-ODN on the innate immune system of the horse: an in-vivo trial
Tosi, Irène ULg; Pirottin, Dimitri ULg; Fievez, Laurence ULg et al

Poster (2015, October 16)

Oligodeoxynucleotides containing cytosine-phosphate-guanosine motifs (CpG-ODN) represent a class of agonists of Toll-like Receptor 9 (TLR9). TLR9 activation induces the secretion of cytokines and the ... [more ▼]

Oligodeoxynucleotides containing cytosine-phosphate-guanosine motifs (CpG-ODN) represent a class of agonists of Toll-like Receptor 9 (TLR9). TLR9 activation induces the secretion of cytokines and the maturation of immune cells, thus initiating both innate and adaptive immune responses. Therefore, CpG-ODN has been investigated in different species as a potential immune-modulator targeting infectious, allergic and neoplastic diseases. It has been administered by nebulisation to RAO-affected horses with promising results. Nonetheless, there is no in-vivo study on the effect of CpG administered systemically to the horse. Therefore, we tested the effect of CpG, given by intramuscular injection, on the equine immune response. Eight horses were used for this study. Five mg/horse were injected to 4 horses at D0 and D7; the other horses received a placebo (PBS). Blood was collected 2 days prior to each injection, then regularly up to D21. A clinical exam was realised daily. Laboratory analyses included haematology, ELISA tests for IFN-alpha, IFN-gamma, TNF-alpha and IL-10 and cytometry analyses for MCHII and CD86 expressions on B-lymphocytes. A cross-over of the 2 groups was realised after 2 months of washout. CpG was well tolerated. Significant transient eosinopenia, monocytosis and leukopenia were observed after CpG injection, while ELISA and cytometry analyses did not reveal any significant modification. This trial represents the first in-vivo study where CpG is administered systemically to healthy horses. Further studies are needed to adjust the dose, the formulation and the sampling schedule and to fully investigate this molecule as potentiel modulator of the equine immune system. [less ▲]

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See detailThe Innate Immune Response of Equine Bronchial Epithelial Cells is Altered by Training
Frellstedt, Linda ULg; Gosset, Philippe; Kervoaze, Gwenola et al

in Veterinary Research (2015), 46(3), 1-12

Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier ... [more ▼]

Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in vitro by an explant method. The innate immune response of EBEC was evaluated in vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral dsRNA, triggers a strong secretion of IFN-β, TNF-α, IL-6 and CXCL8. We further evaluated the EBEC innate immune response in horses that underwent a 4-month-training program. While training had no effect on TLR mRNA expression in EBEC as well as in bronchial biopsies, it increased the production of IFN-β after stimulation with a TLR3 ligand and decreased the secretion of TNF-α and IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be implicated in the increased risk for viral and bacterial infections observed in sport horses. Altogether, we report a successful model for the culture of EBEC that can be applied to the investigation of pathophysiologic conditions in longitudinal studies. [less ▲]

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See detailGeneration of a soluble recombinant trimeric form of bovine CD40L and its potential use as a vaccine adjuvant in cows
Pujol, Julien ULg; Bouillenne, Fabrice ULg; Farnir, Frédéric ULg et al

in Veterinary immunology and immunopathology (2015), 168(1), 1-13

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See detailDevelopment and performance assessment of a qualitative SYBR(R) green real-time PCR assay for the detection of Aspergillus versicolor in indoor air.
Libert, X.; Chasseur, C.; Bladt, S. et al

in Applied Microbiology and Biotechnology (2015), 99(17), 7267-7282

Currently, contamination of indoor environment by fungi and molds is considered as a public health problem. The monitoring of indoor airborne fungal contamination is a common tool to help understanding ... [more ▼]

Currently, contamination of indoor environment by fungi and molds is considered as a public health problem. The monitoring of indoor airborne fungal contamination is a common tool to help understanding the link between fungi in houses and respiratory problems. Classical analytical monitoring methods, based on cultivation and microscopic identification, depend on the growth of the fungi. Consequently, they are biased by difficulties to grow some species on certain culture media and under certain conditions or by noncultivable or dead fungi that can consequently not be identified. However, they could have an impact on human health as they might be allergenic. Since molecular methods do not require a culture step, they seem an excellent alternative for the monitoring of indoor fungal contaminations. As a case study, we developed a SYBR(R) green real-time PCR-based assay for the specific detection and identification of Aspergillus versicolor, which is frequently observed in indoor environment and known to be allergenic. The developed primers amplify a short region of the internal transcribed spacer 1 from the 18S ribosomal DNA complex. Subsequently, the performance of this quantitative polymerase chain reaction (qPCR) method was assessed using specific criteria, including an evaluation of the selectivity, PCR efficiency, dynamic range, and repeatability. The limit of detection was determined to be 1 or 2 copies of genomic DNA of A. versicolor. In order to demonstrate that this SYBR(R) green qPCR assay is a valuable alternative for monitoring indoor fungal contamination with A. versicolor, environmental samples collected in contaminated houses were analyzed and the results were compared to the ones obtained with the traditional methods. [less ▲]

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See detailExpression microarray as a tool to identify candidate blood biomarkers in horses suffering from inflammatory airway disease
Ramery, Eve ULg; Fraipont, Audrey ULg; Art, Tatiana ULg et al

in Veterinary Clinical Pathology (2015), 44(1), 37-46

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires ... [more ▼]

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires sedation. Objectives: The purpose of this study was to identify candidate blood biomarkers of IAD using species-specific expression microarrays. Methods: Horse Gene Expression Microarrays were used to investigate global mRNA expression in circulating leukocytes from healthy and IAD-affected standardbreds and endurance horses. Results: Nine genes were significantly differentially regulated in standardbreds and 61 in endurance horses (P < 0.001). These genes were mainly related to inflammation (eg. ALOX15B, PLA2G12B and PENK), oxidant/antioxidant balance (eg. DUOXA2 and GSTO1-1) and stress (eg. V1aR, GRLF1, Homer-2 and MAOB). DUOXA2, ALOX15B, PLA2G12B, MAOB and GRLF1 variations of expression were further validated by RT-qPCR. The deregulation of the oxidant/antioxidant balance was demonstrated at the protein level by an increase of glutathione peroxidase (GPx) activity in heparinised whole blood of IAD-affected standardbreds (P = 0.0025) and endurance horses (P = 0.0028). There was good correlation (r = 0.7354) between BAL neutrophil percentage and whole blood GPx activity in all horses. Conclusions: There is accumulating evidence that, even when systemic clinical signs are not evident, circulating leukocyte gene expression can reflect responses of other tissues, leading to potential diagnostic applications in the future. Although not specific for IAD, whole blood GPx activity appears to reflect BAL neutrophil percentage. This finding should be further assessed by testing a larger number of horses. [less ▲]

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