References of "Lekeux, Pierre"
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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 (in press)

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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See detailTraining Modifies Innate Immune Responses in Blood Monocytes and in Pulmonary Alveolar Macrophages
Frellstedt, Linda ULg; Waldschmidt, Ingrid; Gosset, Philippe et al

in American Journal of Respiratory Cell and Molecular Biology (2014), 51(1), 135-142

In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs), co-stimulatory and antigen-presenting ... [more ▼]

In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs), co-stimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because the innate immunity plays an essential role in lung defense mechanisms, we aimed to assess the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAM) were collected from horses in an untrained, moderately and intensively trained as well as deconditioned state before and after a strenuous exercise test (SET). The cells were analysed for TLR mRNA expression by real-time PCR in vitro and the cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with lipopolysaccharide (LPS) and a synthetic diacylated lipoprotein (FSL) showed increased cytokine secretion in trained and deconditioned subjects indicating the activation of cells at the systemic level. The production of TNF-alpha and IFN-beta in non-stimulated and stimulated PAM was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection. [less ▲]

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See detailResident lung CD11b+Ly6C- dendritic cells are responsible for allergic airway sensitization to house dust mite in mice
Mesnil, Claire ULg; Sabatel, Catherine ULg; Marichal, Thomas ULg et al

in Proceeding of International Congress of Immunology 2013 (2013)

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See detailTraining modifies the innate immune response both in the airways and in blood in horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

in Proceedings of the ICI (2013)

Lower airway diseases are common problems in sports and racing horses. In humans, exercise has been associated with upper respiratory tract infections due to down-regulated expression of Toll-like ... [more ▼]

Lower airway diseases are common problems in sports and racing horses. In humans, exercise has been associated with upper respiratory tract infections due to down-regulated expression of Toll-like receptors (TLRs), costimulatory and antigen-presenting molecules on monocytes. The objectives of this study were 1) to examine the expression of TLRs in equine bronchial epithelial cells (EBEC) and blood monocytes in untrained and trained horses; 2) to stimulate EBEC and monocytes in vitro with TLR ligands, in order to mimic bacterial/viral infections; 3) to compare the cytokine production of EBEC and monocytes in untrained and trained horses. Bronchial biopsies were taken from 8 horses during lower airway endoscopy at rest and 24 hours after a standardized exercise test (SET). Bronchial epithelial cells were grown in vitro and activated with TLR ligands. Blood monocytes were collected at rest and after the SET. TLR1-TLR9 expression was evaluated via real-time PCR and cytokine production was measured via ELISA. TLR3 and TLR4 expression was modified by training. The expression of TLR2, TLR7 and TLR8 was modified only by strenuous exercise in trained horses. Training had local immuno-suppressive effects shown by a decreased production of TNF-alpha and IFN-beta in EBEC in response to TLR2 and TLR3 ligands. Training also caused a systemic pro-inflammatory response evidenced by increased production of TNF-alpha in monocytes in response to TLR2 and TLR4 ligands. These findings suggest that training and strenuous exercise in trained subjects may result in an increased susceptibility of the lower airway to infections associated with systemic inflammation. [less ▲]

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See detailExercise modifies the innate immune response in equine bronchial epithelial cells
Frellstedt, Linda ULg; Gosset, Philippe; Pirottin, Dimitri ULg et al

in Proceedings of the 3rd Scientific Meeting of the Faculty of Veterinary Medicine (University of Liege - Belgium) (2013)

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See detailDetection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy
Dupuis, Marie-Capucine; Zhang, Zhiyan ULg; Durkin, Keith ULg et al

in Animal Genetics (2013)

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with ... [more ▼]

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN), an important equine upper airway disease compromising performance. A total of 2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs, particularly deletions, were shown to be significantly depleted in genes. Fifty-two of the 67 common CNVRs (frequency ! 1%) were validated by association mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67 common CNVRs were significantly associated with RLN when accounting for multiple testing. However, a duplication on chromosome 10 was detected in 10 cases (representing three breeds) and two unphenotyped parents but in none of the controls. The duplication was embedded in an 8-Mb haplotype shared across breeds. [less ▲]

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See detailMyeloid Hif1alpha counteracts allergic airway sensitization in mice through macrophage-mediated immunoregulation
Toussaint, Marie ULg; Fievez, Laurence ULg; Drion, Pierre ULg et al

in Abstract book of Keystone Symposium "Myeloid Cells: Regulation and Inflammation" (2013)

Hypoxia Inducible Factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid ... [more ▼]

Hypoxia Inducible Factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. In contrast, we observed that mice conditionally deficient for Hif1alpha in myeloid cells display enhanced sensitivity to the development of airway allergy to the experimental allergen ovalbumin as well as to house dust mite antigens. Following allergen exposure, these mice indeed developed enhanced allergen-specific T cell responses due to augmented activation of lung dendritic cells. Further analyses supported the idea that upon allergen exposure, MyD88-dependent upregulation of Hif1alpha boosts the expression of the immunosuppressive cytokine Interleukin (IL)-10 by lung interstitial macrophages. Interstitial macrophage-derived IL-10 in turn counteracts allergen-induced lung dendritic cell activation, consequently preventing the development of allergen-specific T cell responses. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1alpha possesses immunoregulatory functions implicated in the prevention of airway allergy. [less ▲]

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See detailMyeloid hypoxia-inducible factor 1alpha prevents airway allergy in mice through macrophage-mediated immunoregulation
Toussaint, Marie ULg; Fievez, Laurence ULg; Drion, Pierre ULg et al

in Mucosal Immunology (2013), 6(3), 485-97

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid ... [more ▼]

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1alpha in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1alpha boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1alpha-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1alpha possesses immunoregulatory functions implicated in the prevention of airway allergy. [less ▲]

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See detailThe respiratory system: anatomy, physiology, and adaptations to exercise and training
Lekeux, Pierre ULg; Art, Tatiana ULg; Hodgson, David R

in Hodgson, D.R.; McKeever, K.H.; McGowan, C.M. (Eds.) The Athletic Horse. Principles and Practice of Equine Sports Medicine Second Edition (2013)

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See detailTraining-induced decrease of cytokines production by equine alveolar macrophages
Waldschmidt, Ingrid ULg; Frellstedt, Linda ULg; Art, Tatiana ULg et al

in Proceedings of the 6th Congress of the European College of Equine Internal Medicine (ECEIM) (2013)

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See detailInvestigation of the effect of exercise on the innate immunity in horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

Poster (2012, October 19)

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See detailRelease and Innate detection of host cell DNA mediates the adjuvant effects of aluminum salts on adaptive responses
Marichal, Thomas ULg; Ohata, Keichii; Bedoret, Denis et al

in Proceedings of the 1St Winter School Immunology (2012, January)

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See detailMethacholine bronchoprovocation test:a useful ancillary test for diagnosis of hyperresponsiveness in horses ?
Frippiat, Thibault ULg; Frellstedt, Linda ULg; Bustin, Jean-Clément ULg et al

in Proceedings of the European Veterinary Conference - Voorjaarsdagen (2012)

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See detailSerum concentration of surfactant protein D in horses with lower airway inflammation
Richard, Eric; Pitel, Pierre-Hugues; Christmann, Undine et al

in Equine Veterinary Journal (2012), 44

Reasons for performing study: Surfactant protein D (SP-D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man ... [more ▼]

Reasons for performing study: Surfactant protein D (SP-D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man, circulating concentrations of SP-D are routinely used as biomarkers for pulmonary injury. To date, serum SP-D levels have only been investigated in horses in an experimental model of bacterial airway infection. Objectives: To compare serum SP-D concentrations at rest and after exercise in horses with and without inflammatory airway disease (IAD). Methods: Venous blood samples were collected from 42 Standardbred racehorses at rest and 60 min after performing a standardised treadmill exercise test. Tracheal wash and bronchoalveolar lavage fluid (BALF) samples were collected after exercise. Based on BALF cytology, 22 horses were defined as IAD-affected and 20 classified as controls. Serum SP-D concentrations were assessed using a commercially available ELISA kit and statistically compared between groups of horses and sampling times. Results: Serum concentrations of SP-D in IAD-affected horses were significantly higher than those of control horses, both at rest and after exercise. Within the IAD-affected group, no significant correlation was found between serum SP-D concentrations and BALF cytology. Within each group of horses (IAD and control), no significant influence of exercise was found on serum SP-D levels. Conclusions: This is the first study determining serum SP-D concentrations in a noninfectious, naturally occurring form of lower airway inflammation in horses. The results highlight that IAD is associated with a detectable, though moderate, increase of circulating SP-D levels. Potential relevance: Serum concentration of surfactant protein D could represent a potentially valuable and readily accessible blood biomarker of equine lower airway inflammation [less ▲]

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See detailIntérêt du dosage sanguin de la protéine D de surfactant (SP-D) lors d'inflammation des voies respiratoires profondes
Richard, Eric; Pitel, P. H.; Christmann, Undine et al

in Proceedings de la 38ème Journée de la Recherche Equine (2012)

Surfactant protein D (SP-D), mainly synthetised by alveolar type II tells, isone important component of innate pulmonary immunity. The aim of the study was te sompare serum SP-D concentrations in horses ... [more ▼]

Surfactant protein D (SP-D), mainly synthetised by alveolar type II tells, isone important component of innate pulmonary immunity. The aim of the study was te sompare serum SP-D concentrations in horses with and without inflammatory airway disease (IAD). Venous blond samples were collected from 42 Standardbred racehorses at rest and 60 min after performing a standardised treadmill exercise test. Based on bronchoalveolar lavage cytology, 22 horses were defined as IAD-affected and 20 classified as controls. Serum concentrations of SP-D in IAD-affected horses were significantly higher than those of control horses, both at rest and after exercise. Within each group of horses (IAD and control), no significant influence of exercise was found on serum SP-D levels. This is he first study determining serum SP-D concentrations in a noninfectious, naturally occuring form of louver airway inflammation in horses. The results highlight that IAD is associated with a detectable, though moderate, increase of circulating SP-D levels. Serum concentration of surfactant protein D could represent a potentially valuable and readily accessible blond biomarker of equine louver airway inflammation. [less ▲]

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