References of "Bureau, Fabrice"
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See detailRelease of Neutrophils Extracellular Traps as a main trigger for asthma onset
Radermecker, Coraline ULg; Sabatel, Catherine ULg; 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 ▲]

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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 detailRelease of Neutrophils Extracellular Traps as a main trigger for asthma onset
Radermecker, Coraline ULg; Sabatel, Catherine ULg; 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 ▲]

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See detailThe Roles of Spinochromes in Four Shallow Water Tropical Sea Urchins and Their Potential as Bioactive Pharmacological Agents.
Brasseur, Lola; Hennebert, Elise; Fievez, Laurence ULg et al

in Marine Drugs (2017), 15(6),

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin ... [more ▼]

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes in order to test their antibacterial, antioxidant, inflammatory and cytotoxic activities. First, the antibacterial assays show that the use of crude extracts as representatives of antibacterial effects of spinochromes are inaccurate. The assays on purified spinochromes showed a decrease in the growth of four strains with an intensity depending on the spinochromes/bacteria system, revealing the participation of spinochromes in the defense system against microorganisms. Secondly, in the 2,2-diphenyl-1-picrylhydrazyl antioxidant assays, spinochromes show an enhanced activity compared to the positive control. This latter observation suggests their involvement in ultraviolet radiation protection. Third, spinochromes present a pro-inflammatory effect on lipopolysaccharide-stimulated macrophages, highlighting their possible implication in the sea urchin immune system. Finally, cytotoxicity assays based on Trypan blue exclusion, performed in view of their possible future applications as drugs, show a weak cytotoxicity of these compounds against human cells. In conclusion, all results confirm the implication of spinochromes in sea urchin defense mechanisms against their external environment and reveal their potential for pharmacological and agronomical industries. [less ▲]

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See detailDevelopment and performance assessment of a luminex xMAP(R) direct hybridization assay for the detection and identification of indoor air fungal contamination.
Libert, Xavier; Packeu, Ann; Bureau, Fabrice ULg et al

in PLoS ONE (2017), 12(3), 0173390

Considered as a public health problem, indoor fungal contamination is generally monitored using classical protocols based on culturing. However, this culture dependency could influence the ... [more ▼]

Considered as a public health problem, indoor fungal contamination is generally monitored using classical protocols based on culturing. However, this culture dependency could influence the representativeness of the fungal population detected in an analyzed sample as this includes the dead and uncultivable fraction. Moreover, culture-based protocols are often time-consuming. In this context, molecular tools are a powerful alternative, especially those allowing multiplexing. In this study a Luminex xMAP(R) assay was developed for the simultaneous detection of 10 fungal species which are most frequently in indoor air and that may cause health problems. This xMAP(R) assay was found to be sensitive, i.e. its limit of detection is ranging between 0.05 and 0.01 ng of gDNA. The assay was subsequently tested with environmental air samples which were also analyzed with a classical protocol. All the species identified with the classical method were also detected with the xMAP(R) assay, however in a shorter time frame. These results demonstrate that the Luminex xMAP(R) fungal assay developed in this study could contribute to the improvement of public health and specifically to the indoor fungal contamination treatment. [less ▲]

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See detailDiscrimination of three genetically close Aspergillus species by using high resolution melting analysis applied to indoor air as case study.
Libert, Xavier; Packeu, Ann; Bureau, Fabrice ULg et al

in BMC Microbiology (2017), 17(1), 84

BACKGROUND: Indoor air pollution caused by fungal contamination is suspected to have a public health impact. Monitoring of the composition of the indoor airborne fungal contaminants is therefore important ... [more ▼]

BACKGROUND: Indoor air pollution caused by fungal contamination is suspected to have a public health impact. Monitoring of the composition of the indoor airborne fungal contaminants is therefore important. To avoid problems linked to culture-dependent protocols, molecular methods are increasingly being proposed as an alternative. Among these molecular methods, the polymerase chain reaction (PCR) and the real-time PCR are the most frequently used tools for indoor fungal detection. However, even if these tools have demonstrated their appropriate performance, some of them are not able to discriminate between species which are genetically close. A solution to this could be the use of a post-qPCR high resolution melting (HRM) analysis, which would allow the discrimination of these species based on the highly accurate determination of the difference in melting temperature of the obtained amplicon. In this study, we provide a proof-of-concept for this approach, using a dye adapted version of our previously developed qPCR SYBR(R)Green method to detect Aspergillus versicolor in indoor air, an important airborne fungus in terms of occurrence and cause of health problems. Despite the good performance observed for that qPCR method, no discrimination could previously be made between A. versicolor, Aspergillus creber and Aspergillus sydowii. METHODS: In this study, we developed and evaluated an HRM assay for the discrimination between A. versicolor, Aspergillus creber and Aspergillus sydowii. RESULTS: Using HRM analysis, the discrimination of the 3 Aspergillus species could be made. No false positive, nor false negatives were observed during the performance assessment including 20 strains of Aspergillus. The limit of detection was determined for each species i.e., 0.5 pg of gDNA for A. creber and A. sydowii, and 0.1 pg of gDNA for A. versicolor. The HRM analysis was also successfully tested on environmental samples. CONCLUSION: We reported the development of HRM tools for the discrimination of A. versicolor, A. creber and A. sydowii. However, this study could be considered as a study case demonstrating that HRM based on existing qPCR assays, allows a more accurate identification of indoor air contaminants. This contributes to an improved insight in the diversity of indoor airborne fungi and hence, eventually in the causal link with health problems. [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), 23

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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