References of "Desmet, Christophe"
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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 detailAdjuvants targeting the DNA sensing pathways – Alum based adjuvants
Desmet, Christophe ULg

in Ishii, Ken; Tang, Choon Kit (Eds.) Biological DNA Sensor: The Impact of Nucleic Acids on Diseases and Vaccinology (2013)

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See detailIdentification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis
Desmet, Christophe ULg; Gallenne, Tristan; Prieur, Alexandre et al

in Proceedings of the National Academy of Sciences of the United States of America (2013)

Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular ... [more ▼]

Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis. Because Fra-1 often is overexpressed in human metastatic breast cancers and has been shown to control their invasive potential in vitro, we aimed to assess the implication and prognostic significance of the Fra-1-dependent genetic program in breast cancer metastasis and to identify potential Fra-1-dependent therapeutic targets. In several in vivo assays in mice, we demonstrate that stable RNAi depletion of Fra-1 from human breast cancer cells strongly suppresses their ability to metastasize. These results support a clinically important role for Fra-1 and the genetic program it controls. We show that a Fra-1-dependent gene-expression signature accurately predicts recurrence of breast cancer. Furthermore, a synthetic lethal drug screen revealed that antagonists of the adenosine receptor A2B (ADORA2B) are preferentially toxic to breast tumor cells expressing Fra-1. Both RNAi silencing and pharmacologic blockade of ADORA2B inhibited filopodia formation and invasive activity of breast cancer cells and correspondingly reduced tumor outgrowth in the lungs. These data show that Fra-1 activity is causally involved in and is a prognostic indicator of breast cancer metastasis. They suggest that Fra-1 activity predicts responsiveness to inhibition of pharmacologically tractable targets, such as ADORA2B, which may be used for clinical interference of metastatic breast cancer. [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 detailType I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia
Crotta, Stefania; Davidson, Sofia; Mahlakoiv, Tanel et al

in PLoS Pathogens (2013)

The response of cells to virus infection depends on Interferons (IFNs), a group of cytokines which activate the expression of hundreds of genes that help control viral replication inside infected cells ... [more ▼]

The response of cells to virus infection depends on Interferons (IFNs), a group of cytokines which activate the expression of hundreds of genes that help control viral replication inside infected cells. While type I IFN was discovered in 1957, type III IFN (IFNλ, IL-28/29) was characterized recently and is known for its role in the response to hepatitis C virus. Airway epithelia are the primary target of influenza virus, and we studied how infection induces IFNs and which IFN is most important for the epithelial anti-influenza response. We found that infected epithelia detect virus through the cytoplasmic RIG-I/MAVS recognition system, leading to activation of the transcription factor IRF7 and subsequent induction of both type I and III IFNs. All ensuing cellular responses to infection are dependent on the production and secretion of IFNs, as responses are lost in epithelia lacking receptors for both type I and III IFNs. Finally, gene induction is indistinguishable in single receptor-deficient and wild-type cells, indicating that the two IFN systems are completely redundant in epithelia. Thus, influenza infection of airway epithelia induces, via a RIG-I/MAVS/IRF7 dependent pathway, both type I and III IFNs which drive two overlapping and redundant amplification loops to upregulate antiviral genes. [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 detailNeutrophil Extracellular Traps (NET) Entrap and Kill Borrelia burgdorferi sensu stricto Spirochetes and Are not Affected by Ixodes ricinus Tick Saliva.
MENTEN-DEDOYART, Catherine ULg; Faccinetto, Céline; Golovchenko, Maryna et al

in Journal of Immunology (2012), 189(11), 5393-5401

Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). They are transmitted mainly by Ixodes ricinus ticks ... [more ▼]

Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. Neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil’s own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species (ROS) is apparently associated with the onset of NEtosis. Here we describe NETs formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi s.s. spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophiles or it stability. However, it strongly decreased neutrophil ROS production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies were observed trapped in NETs, some of them staining as live cells. This observation could help contribute to a better explanation of erythema migrans. [less ▲]

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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 detailFra-1 target genes as drug targets for treating cancer
Peeper, Daniel Simon; Desmet, Christophe ULg; Reyal, Fabien

Patent (2012)

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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 detailL'ADN du soi, allie du systeme immunitaire pour la fonction adjuvante de l'alun
Marichal, Thomas ULg; Bureau, Fabrice ULg; Desmet, Christophe ULg

in Medecine Sciences : M/S (2012), 28(1), 31-3

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See detailResident CD11b(+)Ly6C(-) Lung 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 PLoS ONE (2012), 7(12), 53242

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway ... [more ▼]

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naive recipients. Transfer of lung CD11c(+)CD11b(+) DCs, but not CD11c(+)CD11b(-)CD103(+) DCs, was sufficient to prime airway allergy. The CD11c(+)CD11b(+) DC subpopulation was composed of CD11c(+)CD11b(+)Ly6C(+) inflammatory monocyte-derived cells, whose numbers increase in the lungs following HDM exposure, and of CD11c(+)CD11b(+)Ly6C(-) DCs, which remain stable. Counterintuitively, only CD11c(+)CD11b(+)Ly6C(-) DCs, and not CD11c(+)CD11b(+)Ly6C(+) DCs, were able to convey antigen to the lymph nodes and induce adaptive T cell responses and subsequent airway allergy. Our results thus support that lung resident non-inflammatory CD11c(+)CD11b(+)Ly6C(-) DCs are the essential inducers of allergic airway sensitization to the common aeroallergen HDM in mice. [less ▲]

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See detailIncreased hypoxia-inducible factor 1alpha expression in lung cells of horses with recurrent airway obstruction.
Toussaint, Marie ULg; Fievez, Laurence ULg; Desmet, Christophe ULg et al

in BMC Veterinary Research (2012), 8(1), 64

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological ... [more ▼]

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. CONCLUSION: Taken together, our results suggest an important role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO. [less ▲]

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