• Eric Muraille's Research Group
  • Eric Muraille's Research Group
  • Eric Muraille's Research Group

Publications

Quels futurs modes d'experimentation pour les sciences de la vie ?
Interview FNRS
L’expérimentation est la « substantifique moelle » de la recherche et de la méthode scientifique. Pratiquée depuis des siècles, elle a considérablement évolué et s’est diversifiée ces dernières décennies, singulièrement dans les sciences de la vie et de la santé. Quelles en sont les perspectives à moyen et long terme ? C’est la question à laquelle ont répondu trois scientifiques particulièrement … expérimentés : Agnès Noël, Alban de Kerchove d’Exaerde, Eric Muraille
Post date: 8 months 2 weeks ago
La Viande cultivée s'approche lentement de nos assiettes
Interview Paris Match
La viande d’élevage va-t-elle être remplacée par de la « viande » fabriquée, in vitro, dans des bioréacteurs ? Souvent financées par des investisseurs déjà présents dans l’agrobusiness, quelque 200 start-up dans le monde tentent de mettre au point le processus industriel qui permettrait cette révolution alimentaire.Le biologiste Eric Muraille (ULB) questionne un certain discours technico-optimiste relatif à « cette pâte de cellules qui imite la viande »
Post date: 8 months 2 weeks ago
Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation
Collectif
La Libre, April 3, 2023
Post date: 11 months 2 weeks ago
Carta Academica - Va-t-on censurer la science au nom de la justice sociale?
Eric Muraille
Le Soir, February 12, 2023
Post date: 1 year 1 month ago
COP27: l’équité au détriment du bien commun?
Eric Muraille, Philippe Naccache
Le Soir, December 2022
Post date: 1 year 1 month ago
Is liberal governance unable to deal with global threats?
Eric Muraille, Julien Pillot, Philippe Naccache
The Conversation. November,  2022
Post date: 1 year 1 month ago
Les pionniers de la biologie ont-ils participé à la construction du racisme ?
Eric Muraille, Céline Rase
The Conversation. November 22,  2022
Post date: 1 year 1 month ago
La révolution microbienne racontée par Hector Lebrun, témoin privilégié du XIXᵉ siècle
Eric Muraille, Céline Rase
The Conversation. September 22,  2022
Post date: 1 year 1 month ago
Genome-wide analysis of Brucella melitensis genes required throughout intranasal infection in mice
Potemberg G, Demars A, Barbieux E, Reboul A, Stubbe F-X, Gallia, M, Lagneaux M, Comein A, Denis O, Pérez-Morga D, Vanderwinden J-M, De Bolle X, Muraille E
Brucellae are facultative intracellular Gram-negative coccobacilli that chronically infect various mammals and cause brucellosis. Human brucellosis is among the most common bacterial zoonoses and the vast majority of cases are attributed to B. melitensis. Using transposon sequencing (Tn-seq) analysis, we showed that among 3369 predicted genes of the B. melitensis genome, 861 are required for optimal growth in rich medium and 186 additional genes appeared necessary for survival of B. melitensis in RAW 264.7 macrophages in vitro. As the mucosal immune system represents the first defense against Brucella infection, we investigated the early phase of pulmonary infection in mice. In situ analysis at the single cell level indicates a succession of killing and growth phases, followed by heterogenous proliferation of B. melitensis in alveolar macrophages during the first 48 hours of infection. Tn-seq analysis identified 94 additional genes that are required for survival in the lung at 48 hours post infection. Among them, 42 genes are common to RAW 264.7 macrophages and the lung conditions, including the T4SS and purine synthesis genes. But 52 genes are not identified in RAW 264.7 macrophages, including genes implicated in lipopolysaccharide (LPS) biosynthesis, methionine transport, tryptophan synthesis as well as fatty acid and carbohydrate metabolism. Interestingly, genes implicated in LPS synthesis and β oxidation of fatty acids are no longer required in Interleukin (IL)-17RA-/- mice and asthmatic mice, respectively. This demonstrates that the immune status determines which genes are required for optimal survival and growth of B. melitensis in vivo. PLoS Pathog. 18(6): e1010621, 2022
Post date: 1 year 1 month ago
The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells
Luizet JB, Raymond J, Lacerda TLS, Barbieux E, Kambarev S, Bonici M, Lembo F, Willemart K, Borg JP, Celli J, Gérard FCA, Muraille E, Gorvel JP, Salcedo SP
Proc Natl Acad Sci U S A.  118(32): e2105324118, 2021
Post date: 1 year 1 month ago
PdeA is required for the rod shape morphology of Brucella abortus
Reboul A, Carlier E, Stubbe FX, Barbieux E, Demars A, Ong PTA, Gerodez A, Muraille E, De Bolle X
Mol Microbiol.  116(6):1449-1463, 2021, doi: 10.1111/mmi.14833
Post date: 1 year 1 month ago
Promoting health in a globalized world requires adopting a One Health perspective
Eric Muraille
Glob Health Promot.  28(3):3-5, 2021, doi: 10.1177/17579759211035070
Post date: 1 year 1 month ago
Is Antibody-Dependent Enhancement of Trypanosoma cruzi Infection Contributing to Congenital/Neonatal Chagas Disease?
Carlier Y, Truyens C, Muraille E.
Front Immunol.  12:723516, 2021, doi: 10.3389/fimmu.2021.723516.
Post date: 1 year 1 month ago
Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice
Demars A, Vitali A, Comein A, Carlier E, Azouz A, Goriely S, Smout J, Flamand V, Van Gysel M, Wouters J, Abendroth J, Edwards TE, Machelart A, Hoffmann E, Brodin P, De Bolle X, Muraille E.
Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene (Acod1; also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to B. melitensis infection at 24 hours post-infection. Upregulation of Acod1 was confirmed by RT-qPCR in lungs infected with B. melitensis and B. abortus. We observed that Acod1-/- C57BL/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following B. melitensis or B. abortus infection, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on Brucella growth in vitro. Interestingly, structural analysis suggests the binding of itaconate into the binding site of B. abortus isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant ΔaceA B. abortus in vitro. Finally, we observed that, unlike the wt strain, the ΔaceA B. abortus strain multiplies similarly in wt and Acod1-/- C57BL/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs. PLoS Pathog. 17(9):e1009887, 2021, doi: 10.1371/journal.ppat.1009887
Post date: 1 year 1 month ago
Comment les microbes réussissent à échapper aux vaccins
Eric Muraille
The Conversation. January 27,  2021
Post date: 1 year 1 month ago
Carta Academica - Nous avons breveté le soleil
Eric Muraille
Le Soir. May 22,  2021
Post date: 1 year 1 month ago
Didier Raoult, le postmodernisme en étendard
Eric Muraille, Alban de Kerchove d'Exaerde, Bernard Feltz
The Conversation. Aout 24,  2021
Post date: 1 year 1 month ago
L’approche One Health : un changement de paradigme indispensable en santé publique
Eric Muraille
Education Santé. October,  2021
Post date: 1 year 1 month ago
Pourquoi l’Europe veut interdire l’expérimentation animale et avec quelles conséquences ?
Eric Muraille
The Conversation. October 26,  2021
Post date: 1 year 1 month ago
L'accroissement des comportements égoïstes peut mener à l'effondrement de la société
Collectif
Le Vif. Opinion. November 24,  2021
Post date: 1 year 1 month ago
De la vaccination à la lutte climatique, l’absolue nécessité de réaffirmer le rôle régulateur de l’Etat
Serge Guérin, Eric Muraille, Philippe Naccache, Julien Pillot
Le Monde. Tribune. November 30,  2021
Post date: 1 year 1 month ago
Preparing for a responsible lockdown exit strategy.
Gilbert M, Dewatripont M, Muraille E, Platteau JP, Goldman M.
Nat Med. 2020, 26(5):643-644. doi: 10.1038/s41591-020-0871-y
Post date: 1 year 1 month ago
Ethical control of innovation in a globalized and liberal world: Is good science still science
Eric Muraille
The independence of science was long seen as of prime importance. This position has become less common today. The perception of scientific research as a public service has led to the opinion that it must be accountable to citizens and produce knowledge and innovation that meet their expectations. Numerous authors have voiced the need for anticipatory ethical control of innovation focusing on the scientific research process. This control is considered as the must-have guarantee for "good science." The current article attempts to trace the ideological origins of the ethical control of innovation, examines its effectiveness against the challenge of globalization and technology-derived major threats and its compatibility with scientific methodology. It also suggests ways to both regulate the innovation process and preserve the independence of science. On the whole, we conclude that truly effective ethical regulation of innovation, i.e. one that protects the greatest number from its adverse effects, is achieved first and foremost by questioning our liberal economic model and the place given to science in our societies. Endeavour. 100709, 2020. doi: 10.1016/j.endeavour.2020.100709
Post date: 1 year 1 month ago
A Critical Blimp-1-Dependent IL-10 Regulatory Pathway in T Cells Protects From a Lethal Pro-inflammatory Cytokine Storm During Acute Experimental Trypanosoma brucei Infection
De Trez, C., Stijlemans, B., Bockstal, V., Cnops, J., Korf, H., Van Snick, J., Caljon, G., Muraille, E., Humphreys I.R., Boon, L., Van Ginderachter, J.A., Magez, S
Frontiers in Immunology.  11:1085, 2020
Post date: 1 year 1 month ago
Les épidémies sont inévitables, apprenons à les anticiper
Eric Muraille
The Conversation. March 22,  2020
Post date: 1 year 1 month ago
Rapidly identifying workers who are immune to COVID-19 and virus-free is a priority for restarting the economy
Dewatripont, M., Goldman, M., Muraille, E., Platteau, J-P
VOX CEPR Policy. March 23,  2020
Post date: 1 year 1 month ago
There is no evidence that the coronavirus was created in a laboratory
Eric Muraille
The Conversation. April 5,  2020
Post date: 1 year 1 month ago
Covid-19 : comment une stratégie de doubles tests permettrait de sortir du confinement et de relancer l’économie
Muraille, E., Platteau, J-P., Dewatripont, M., Goldman, M.
The Conversation. April 19,  2020
Post date: 1 year 1 month ago
Covid-19 : comment fonctionnent les tests et quelles sont leurs utilités
Eric Muraille
The Conversation. April 22,  2020
Post date: 1 year 1 month ago
The ‘One Health’ concept must prevail to allow us to prevent pandemics
Muraille, E., Jacques Godfroid
The Conversation. June 24,  2020
Post date: 1 year 1 month ago
Fact check : Est-il possible de développer un vaccin contre le Covid-19 en moins d'un an ?
Eric Muraille
The Conversation. July 5,  2020
Post date: 1 year 1 month ago
Hold-up sur la recherche biomédicale en Wallonie
Eric Muraille
Le Vif. December 3,  2020
Post date: 1 year 1 month ago
La ministre Tellier "soumise" aux universités sur l’expérimentation animale ? La désinformation pure et simple de Gaia et S.E.A
Eric Muraille
La Libre. December 13,  2020
Post date: 1 year 1 month ago
Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis
Machelart A, Salzano G, Li X, Demars A, Debrie AS, Menendez-Miranda M, Pancani E, Jouny S, Hoffmann E, Deboosere N, Belhaouane I, Rouanet C, Simar S, Talahari S, Giannini V, Villemagne B, Flipo M, Brosch R, Nesslany F, Deprez B, Muraille E, Locht C, Baula
Nat Commun. 2019, 24;10(1):4847. doi: 10.1038/s41467-019-12516-8
Post date: 1 year 1 month ago
Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus
Poncin, K., Roba, A., Jimmidi, R., Potemberg, G., Fioravanti, A., Francis, N., Willemart, K., Zeippen, N., Machelart, A., Biondi, E. E., Muraille, E., Vincent, S. S., De Bolle, X
Nat Commun. 2019, 24;10(1):4847. doi: 10.1038/s41467-019-12516-8
Post date: 1 year 1 month ago
Cultured’ meat could create more problems than it solves
Eric Muraille
The Conversation. November 18,  2019
Post date: 1 year 1 month ago
Vaccins vivants atténués : pourquoi il ne faut pas renoncer à les utiliser
Eric Muraille
The Conversation. 23 juillet 2019
Post date: 4 years 8 months ago
L’expérimentation animale : toujours une nécessité pour la santé animale et humaine
Collectif
Opinion, Le Soir, 9 juillet 2019
Post date: 4 years 8 months ago
Route of Infection Strongly Impacts the Host-Pathogen Relationship
Aurore Demars, Aurore Lison, Arnaud Machelart, Margaux Van Vyve, Georges Potemberg, Jean-Marie Vanderwinden, Xavier De Bolle, Jean-Jacques Letesson and Eric Muraille
Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80+ myeloid cells. In striking contrast, infected Ly6G+ neutrophils and CD140a+ fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the ΔvirB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4+ T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. γδ+ T cells appear able to compensate for the absence of αβ+ T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship. Frontiers in Imunology. 2019
Post date: 4 years 8 months ago
Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis
Machelart A, Salzano G, Li X, Demars A, Debrie AS, Menendez-Miranda M, Pancani E, Jouny S, Hoffmann E, Deboosere N, Belhaouane I, Rouanet C, Simar S, Talahari S, Giannini V, Villemagne B, Flipo M, Brosch R, Nesslany F, Deprez B, Muraille E, et al.
ACS Nano. 2019, 13(4):3992-4007.
Post date: 4 years 9 months ago
Vers une véganisation de la nature ?
Eric Muraille, Alban de Kerchove d’Exaerde, Jean-Philippe Vielle Calzada
Opinion, La Libre, 7 février 2019
Post date: 5 years 1 month ago
Pourquoi la diversité biologique est la condition de notre survie
Eric Muraille
The Conversation. 15 novembre 2018
Post date: 5 years 2 months ago
Expérimentation animale: la recette d'une polémique scientifique
Eric Muraille
Opinion, La Libre, 20 aout 2018
Post date: 5 years 7 months ago
Allergic Asthma Favors Brucella Growth in the Lungs of Infected Mice
Arnaud Machelart, Georges Potemberg, Laurye Van Maele, Aurore Demars, Maxime Lagneaux, Carl De Trez, Catherine Sabatel, Fabrice Bureau, Sofie De Prins, Pauline Percier, Olivier Denis, Fabienne Jurion, Marta Romano, Jean-Marie Vanderwinden, Eric Muraille
Allergic asthma is a chronic Th2 inflammatory disease of the lower airways affecting a growing number of people worldwide. The impact of infections and microbiota composition on allergic asthma has been investigated frequently. Until now, however, there have been few attempts to investigate the impact of asthma on the control of infectious microorganisms and the underlying mechanisms. In this work, we characterize the consequences of allergic asthma on intranasal (i.n.) infection by Brucella bacteria in mice. We observed that i.n. sensitization with extracts of the house dust mite Dermatophagoides farinae or the mold Alternaria alternata (Alt) significantly increased the number of Brucella melitensis, Brucella suis, and Brucella abortus in the lungs of infected mice. Microscopic analysis showed dense aggregates of infected cells composed mainly of alveolar macrophages (CD11c+ F4/80+ MHCII+) surrounded by neutrophils (Ly-6G+). Asthma-induced Brucella susceptibility appears to be dependent on CD4+ T cells, the IL-4/STAT6 signaling pathway and IL-10, and is maintained in IL-12- and IFN-γR-deficient mice. The effects of the Alt sensitization protocol were also tested on Streptococcus pneumoniae and Mycobacterium tuberculosis pulmonary infections. Surprisingly, we observed that Alt sensitization strongly increases the survival of S. pneumoniae infected mice by a T cell and STAT6 independent signaling pathway. In contrast, the course of M. tuberculosis infection is not affected in the lungs of sensitized mice. Our work demonstrates that the impact of the same allergic sensitization protocol can be neutral, negative, or positive with regard to the resistance of mice to bacterial infection, depending on the bacterial species. Frontiers in Imunology. 2018
Post date: 5 years 7 months ago
Sale temps pour la science
Eric Muraille
Sale temps pour la science. Jouant sur l’émotion et des pseudo-controverses scientifiques, des associations prétendent à l’inutilité de l’usage d’animaux dans la recherche scientifique. Une campagne de dénigrement qui en rappelle d’autres. Opinion. La Libre. 1 aout 2018
Post date: 5 years 7 months ago
Antispécisme et véganisme constituent-ils des projets de sociétés réalistes ?
Eric Muraille
The conversation. 5 juillet 2018
Post date: 5 years 8 months ago
L'expérimentation animale en question
Eric Muraille, Alban de Kerchove d'Exaerde
Exposé "L'expérimentation animale en question", Académie Royale de Médecine de Belgique, le 8 mai 2018.
Post date: 5 years 10 months ago
L’expérimentation animale reste indispensable
collectif
Opinion. La Libre. 22 novembre 2017
Post date: 5 years 10 months ago
La souris, le patient, et le faux expert. Décryptage d'une mystification.
collectif
Opinion. Le Vif. 27 avril 2018.
Post date: 5 years 10 months ago
Le code Wallon du bien être animal facteur de délocalisation
Eric Muraille
Opinion. La Libre. 29 mars 2018
Post date: 5 years 11 months ago
L'expérimentation animale ne se fait pas en dehors de tout contrôle
Eric Muraille
Opinion. La Libre. 11 avril 2018.
Post date: 5 years 11 months ago
STAT6 Mediates Footpad Immunopathology in the Absence of IL-12p40 Following Infection of Susceptible BALB/c Mice With Leishmania major
Florence Kauffmann, Elyn Meert, Kaat de Jonge, Yvon Elkrim, Delphine Hanot Mambres, Olivier Denis, Eric Muraille, Stefan Magez and Carl De Trez
Frontiers in Immunology, 2018
Post date: 6 years 6 days ago
Diversity Generator Mechanisms Are Essential Components of Biological Systems: The Two Queen Hypothesis
Eric Muraille
Diversity is widely known to fuel adaptation and evolutionary processes and increase robustness at the population, species and ecosystem levels. The Neo-Darwinian paradigm proposes that the diversity of biological entities is the consequence of genetic changes arising spontaneously and randomly, without regard for their usefulness. However, a growing body of evidence demonstrates that the evolutionary process has shaped mechanisms, such as horizontal gene transfer mechanisms, meiosis and the adaptive immune system, which has resulted in the regulated generation of diversity among populations. Though their origins are unrelated, these diversity generator (DG) mechanisms share common functional properties. They (i) contribute to the great unpredictability of the composition and/or behavior of biological systems, (ii) favor robustness and collectivism among populations and (iii) operate mainly by manipulating the systems that control the interaction of living beings with their environment. The definition proposed here for DGs is based on these properties and can be used to identify them according to function. Interestingly, prokaryotic DGs appear to be mainly reactive, as they generate diversity in response to environmental stress. They are involved in the widely described Red Queen/arms race/Cairnsian dynamic. The emergence of multicellular organisms harboring K selection traits (longer reproductive life cycle and smaller population size) has led to the acquisition of a new class of DGs that act anticipatively to stress pressures and generate a distinct dynamic called the "White Queen" here. The existence of DGs leads to the view of evolution as a more "intelligent" and Lamarckian-like process. Their repeated selection during evolution could be a neglected example of convergent evolution and suggests that some parts of the evolutionary process are tightly constrained by ecological factors, such as the population size, the generation time and the intensity of selective pressure. The ubiquity of DGs also suggests that regulated auto-generation of diversity is a fundamental property of life. Frontiers in Microbiology. 2018
Post date: 6 years 1 month ago
Chronic Brucella Infection Induces Selective and Persistent Interferon Gamma-Dependent Alterations of Marginal Zone Macrophages in the Spleen
Machelart A, Khadrawi A, Demars A, Willemart K, De Trez C, Letesson JJ, Muraille E
The spleen is known as an important filter for blood-borne pathogens that are trapped by specialized macrophages in the marginal zone (MZ): the CD209+ MZ macrophages (MZMs) and the CD169+ marginal metallophilic macrophages (MMMs). Acute systemic infection strongly impacts MZ populations and the location of T and B lymphocytes. This phenomenon has been linked to reduced chemokine secretion by stromal cells. Brucella spp. are the causative agent of brucellosis, a widespread zoonotic disease. Here, we used Brucella melitensis infection as a model to investigate the impact of chronic stealth infection on splenic MZ macrophage populations. During the late phase of Brucella infection, we observed a loss of both MZMs and MMMs, with a durable disappearance of MZMs, leading to a reduction of the ability of the spleen to take up soluble antigens, beads, and unrelated bacteria. This effect appears to be selective as every other lymphoid and myeloid population analyzed increased during infection, which was also observed following Brucella abortus and Brucella suis infection. Comparison of wild-type and deficient mice suggested that MZ macrophage population loss is dependent on interferon gamma (IFN-γ) receptor but independent of T cells or tumor necrosis factor alpha receptor 1 (TNF-αR1) signaling pathways and is not correlated to an alteration of CCL19, CCL21, and CXCL13 chemokine mRNA expression. Our results suggest that MZ macrophage populations are particularly sensitive to persistent low-level IFN-γ-mediated inflammation and that Brucella infection could reduce the ability of the spleen to perform certain MZM- and MMM-dependent tasks, such as antigen delivery to lymphocytes and control of systemic infection. Infect Immun. 2017;85(11).
Post date: 6 years 4 months ago
La gestion de la coopération au sein des systèmes biologiques
Eric Muraille
Bien que les relations symbiotiques de type coopératives soient ubiquitaires dans la nature et leur intérêt pour la survie des entités biologiques bien établi, la manière dont celles-ci ont été sélectionnées au cours de l'évolution trouble et divise les théoriciens de l'évolution depuis des décennies. Une association coopérative entre individus d'une même espèce ou d'espèces différentes, nous parlerons de consortium, génère des biens communs, par exemple des nutriments ou des mécanismes de protections. Un partenaire égoïste peut, en accaparant sans contrepartie ces biens, augmenter considérablement son avantage sélectif aux détriments des individus coopérateurs. Quand le nombre d'individus agissant de manière égoïste dépasse un point critique, la survie du consortium est menacée. Comment éviter cette "tragédie des communs"? Cet article propose une synthèse originale des principales théories expliquant la stabilisation des relations coopératives entre individus non apparentés au cours de l'évolution. Dans de nombreux systèmes biologiques, les gains provenant des processus coopératifs auraient favorisé au cours de l'évolution la sélection de mécanismes de contrôle social visant à la neutralisation ou à l’exclusion des partenaires égoïstes. Ces mécanismes seraient à l'origine de l'instauration de normes sociales au sein des systèmes biologiques. Les causes de la sélection des religions durant l'évolution humaine sont analysées dans ce cadre conceptuel. Revue des Questions Scientifiques, 2017, 188 (3) : 331-372
Post date: 6 years 5 months ago
The nonspecific face of adaptive immunity
Muraille E, Goriely S
Memory T cells generated by infection or immunization persist in the organism and mediate specific protection upon rechallenge with microbial pathogens expressing the same molecular structures. However, multiple lines of evidence indicate that previously encountered or persisting pathogens influence the immune response to unrelated pathogens. We describe the acquisition of non-antigen specific memory features by both innate and adaptive immune cells explaining these phenomena. We also focus on the different mechanisms (homeostatic or inflammatory cytokine-driven) that lead to acquisition of memory phenotype and functions by antigen-inexperienced T lymphocytes. We discuss the implications of these new concepts for host defense, auto-immunity and vaccination strategies. Curr Opin Immunol. 2017;48:38-43.
Post date: 6 years 6 months ago
Trypanosoma Infection Favors Brucella Elimination via IL-12/IFNγ-Dependent Pathways
Machelart A, Van Vyve M, Potemberg G, Demars A, De Trez C, Tima HG, Vanwalleghem G, Romano M, Truyens C, Letesson JJ, Muraille E
This study develops an original co-infection model in mice using Brucella melitensis, the most frequent cause of human brucellosis, and Trypanosoma brucei, the agent of African trypanosomiasis. Although the immunosuppressive effects of T. brucei in natural hosts and mice models are well established, we observed that the injection of T. brucei in mice chronically infected with B. melitensis induces a drastic reduction in the number of B. melitensis in the spleen, the main reservoir of the infection. Similar results are obtained with Brucella abortus- and Brucella suis-infected mice and B. melitensis-infected mice co-infected with Trypanosoma cruzi, demonstrating that this phenomenon is not due to antigenic cross-reactivity. Comparison of co-infected wild-type and genetically deficient mice showed that Brucella elimination required functional IL-12p35/IFNγ signaling pathways and the presence of CD4+ T cells. However, the impact of wild type and an attenuated mutant of T. brucei on B. melitensis were similar, suggesting that a chronic intense inflammatory reaction is not required to eliminate B. melitensis. Finally, we also tested the impact of T. brucei infection on the course of Mycobacterium tuberculosis infection. Although T. brucei strongly increases the frequency of IFNγ+CD4+ T cells, it does not ameliorate the control of M. tuberculosis infection, suggesting that it is not controlled by the same effector mechanisms as Brucella. Thus, whereas T. brucei infections are commonly viewed as immunosuppressive and pathogenic, our data suggest that these parasites can specifically affect the immune control of Brucella infection, with benefits for the host. Front. Immunol., 31 July 2017
Post date: 6 years 7 months ago
Erythritol Availability in Bovine, Murine and Human Models Highlights a Potential Role for the Host Aldose Reductase during Brucella Infection
Barbier T, Machelart A, Zúñiga-Ripa A, Plovier H, Hougardy C, Lobet E, Willemart K, Muraille E, De Bolle X, Van Schaftingen E, Moriyón I, Letesson JJ
Front Microbiol. 2017;8:1088.
Post date: 6 years 8 months ago
L’expérimentation animale en question
Eric Muraille
De nombreuses associations militant en faveur des droits des animaux présentent l'expérimentation animale comme une pratique moralement inacceptable, inutile et en conséquence, à proscrire. De manière surprenante, ce message trouve un écho grandissant dans la population et chez les représentants politiques. Il est pourtant aisé de démontrer que l'expérimentation animale est une étape essentielle et incontournable de la recherche fondamentale en biologie et médecine et qu'elle constitue une importante source d'innovation en santé humaine et animale. S'en priver reviendrait à amputer les sciences du vivant d'un de leurs principaux outil d'investigation. Néanmoins, le refus de l'expérimentation animale est en passe de devenir chez un nombre croissant d'individus un "marqueur identitaire", au même titre que le refus des organismes génétiquement modifiés ou de la vaccination. Cette polarisation empêche toute réflexion critique et débat rationnel sur le sujet, laissant le champ libre à la désinformation. Cet article vise à informer sur les origines historiques de l'expérimentation animale, son importance en recherche fondamentale, ses apports scientifiques et sociétaux ainsi que son encadrement légal, en vue de donner aux citoyens la possibilité de se faire un avis rationnel sur un enjeu de société majeur. Revue des Questions Scientifiques, 2017, 188 (2) : 129-156
Post date: 6 years 8 months ago
Investigation of inflammatory and allergic responses to common mold species: Results from in vitro experiments, from a mouse model of asthma, and from a group of asthmatic patients
Vincent M, Percier P, De Prins S, Huygen K, Potemberg G, Muraille E, Romano M, Michel O, Denis O
Indoor Air. 2017, doi: 10.1111/ina.12385
Post date: 6 years 8 months ago
Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo
De Smedt T, Pajak B, Muraille E, Lespagnard L, Heinen E, De Baetselier P, Urbain J, Leo O, Moser M
J Exp Med. 1996  184(4):1413-24
Post date: 7 years 4 months ago
Glucocorticoids down-regulate dendritic cell function in vitro and in vivo
Moser M, De Smedt T, Sornasse T, Tielemans F, Chentoufi AA, Muraille E, Van Mechelen M, Urbain J, Leo O
Eur J Immunol. 1995  25(10):2818-24.
Post date: 7 years 4 months ago
Endogenous interleukin-12 is critical for controlling the late but not the early stage of Leishmania mexicana infection in C57BL/6 mice
Aguilar Torrentera F, Laman JD, Van Meurs M, Adorini L, Muraille E, Carlier Y
Infect Immun. 2002  70(9):5075-80.
Post date: 7 years 4 months ago
Bacterial c-di-GMP is an immunostimulatory molecule
Karaolis DK, Means TK, Yang D, Takahashi M, Yoshimura T, Muraille E, Philpott D, Schroeder JT, Hyodo M, Hayakawa Y, Talbot BG, Brouillette E, Malouin F
J Immunol. 2007  178(4):2171-81
Post date: 7 years 4 months ago
Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF
Gatot JS, Gioia R, Chau TL, Patrascu F, Warnier M, Close P, Chapelle JP, Muraille E, Brown K, Siebenlist U, Piette J, Dejardin E, Chariot A
J Biol Chem. 2007  282(43):31131-46
Post date: 7 years 4 months ago
Normal development and function of dendritic cells in mice lacking IDO-1 expression.
de Faudeur G, de Trez C, Muraille E, Leo O
Immunol Lett. 2008  118(1):21-9. doi: 10.1016/j.imlet.2008.02.006
Post date: 7 years 4 months ago
DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4.
Tanaka T, Legat A, Adam E, Steuve J, Gatot JS, Vandenbranden M, Ulianov L, Lonez C, Ruysschaert JM, Muraille E, Tuynder M, Goldman M, Jacquet A
Eur J Immunol. 2008  38(5):1351-7. doi: 10.1002/eji.200737998
Post date: 7 years 4 months ago
Immunomodulatory properties of Lactobacillus plantarum and its use as a recombinant vaccine against mite allergy
Rigaux P, Daniel C, Hisbergues M, Muraille E, Hols P, Pot B, Pestel J, Jacquet A
Allergy. 2009  64(3):406-14. doi: 10.1111/j.1398-9995.2008.01825.x.
Post date: 7 years 4 months ago
Probiotic Escherichia coli Nissle 1917 activates DC and prevents house dust mite allergy through a TLR4-dependent pathway
Adam E, Delbrassine L, Bouillot C, Reynders V, Mailleux AC, Muraille E, Jacquet A
Eur J Immunol. 2010  40(7):1995-2005. doi: 10.1002/eji.200939913.
Post date: 7 years 4 months ago
Complete Genome Sequence of the Escherichia coli PMV-1 Strain, a Model Extraintestinal Pathogenic E. coli Strain Used for Host-Pathogen Interaction Studies
Peris-Bondia F, Muraille E, Van Melderen L
Genome Announc. 2013  1(5). pii: e00913-13.
Post date: 7 years 4 months ago
In vivo characterization of two additional Leishmania donovani strains using the murine and hamster model
Kauffmann F, Dumetz F, Hendrickx S, Muraille E, Dujardin JC, Maes L, Magez S, De Trez C
Parasite Immunol. 2016  38(5):290-302.
Post date: 7 years 4 months ago
Maintenance of B cells during chronic murine Trypanosoma brucei gambiense infection
Cnops J, Kauffmann F, De Trez C, Baltz T, Keirsse J, Radwanska M, Muraille E, Magez S.
Parasite Immunol. 2016  38(10):642-647. doi: 10.1111/pim.12344
Post date: 7 years 4 months ago
Carbohydrate-bearing cell surface receptors involved in innate immunity: interleukin-12 induction by mitogenic and nonmitogenic lectins
Muraille E, Pajak B, Urbain J, Leo O.
Cell Immunol. 1999  10;191(1):1-9.
Post date: 7 years 4 months ago
Downregulation of antigen-presenting cell functions after administration of mitogenic anti-CD3 monoclonal antibodies in mice
Muraille E, Andris F, Pajak B, Wissing KM, De Smedt T, Desalle F, Goldman M, Alegre ML, Urbain J, Moser M, Leo O
Blood. 1999 Dec  94(12):4347-57.
Post date: 7 years 4 months ago
Co-stimulation lowers the threshold for activation of naive T cells by bacterial superantigens
Muraille EM, De Becker G, Bakkus M, Thielemans K, Urbain J, Moser M, Leo O
Int Immunol. 1995  7(2):295-304
Post date: 7 years 4 months ago
Activation of murine T cells by bacterial superantigens requires B7-mediated costimulation
Muraille E, De Smedt T, Thielemans K, Urbain J, Moser M, Leo O
Cell Immunol. 1995  162(2):315-20
Post date: 7 years 4 months ago
B7.2 provides co-stimulatory functions in vivo in response to staphylococcal enterotoxin B
Muraille E, De Smedt T, Urbain J, Moser M, Leo O
Eur J Immunol. 1995  25(7):2111-4
Post date: 7 years 4 months ago
Costimulation regulates the kinetics of interleukin-2 response to bacterial superantigens
Muraille E, Devos S, Thielemans K, Urbain J, Moser M, Leo O
Immunology. 1996  89(2):245-9
Post date: 7 years 4 months ago
Staphylococcal enterotoxin B induces an early and transient state of immunosuppression characterized by V beta-unrestricted T cell unresponsiveness and defective antigen-presenting cell functions
Muraille E, De Smedt T, Andris F, Pajak B, Armant M, Urbain J, Moser M, Leo O
J Immunol. 1997  158(6):2638-47 Bacterial superantigen
Post date: 7 years 4 months ago
Role and regulation of IL-12 in the in vivo response to staphylococcal enterotoxin B
Muraille E, Pajak B, Urbain J, Moser M, Leo O
Int Immunol. 1999  11(9):1403-10 BACTERIAL SUPERANTIGEN
Post date: 7 years 4 months ago
T cell-dependent maturation of dendritic cells in response to bacterial superantigens
Muraille E, De Trez C, Pajak B, Brait M, Urbain J, Leo O
J Immunol. 2002  168(9):4352-60
Post date: 7 years 4 months ago
Distribution of the src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells
Muraille E, Pesesse X, Kuntz C, Erneux C
Biochem J. 1999  342 Pt 3:697-705
Post date: 7 years 4 months ago
The SH2 domain containing inositol 5-phosphatase SHIP2 associates to the immunoreceptor tyrosine-based inhibition motif of Fc gammaRIIB in B cells under negative signaling
Muraille E, Bruhns P, Pesesse X, Daëron M, Erneux C
Immunol Lett. 2000  72(1):7-15
Post date: 7 years 4 months ago
The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice
Muraille E, Dassesse D, Vanderwinden JM, Cremer H, Rogister B, Erneux C, Schiffmann SN
Neuroscience. 2001  105(4):1019-30
Post date: 7 years 4 months ago
TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-beta, but not MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis in vivo
De Trez C, Pajak B, Brait M, Glaichenhaus N, Urbain J, Moser M, Lauvau G, Muraille E
J Immunol. 2005 175(2):839-46
Post date: 7 years 4 months ago
Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes
Muraille E, Giannino R, Guirnalda P, Leiner I, Jung S, Pamer EG, Lauvau G
Eur J Immunol. 2005 35(5):1463-71  
Post date: 7 years 4 months ago
Cytosolic expression of SecA2 is a prerequisite for long-term protective immunity
Muraille E, Narni-Mancinelli E, Gounon P, Bassand D, Glaichenhaus N, Lenz LL, Lauvau G
Cell Microbiol. 2007 9(6):1445-54
Post date: 7 years 4 months ago
Genetically resistant mice lacking MyD88-adapter protein display a high susceptibility to Leishmania major infection associated with a polarized Th2 response
Muraille E, De Trez C, Brait M, De Baetselier P, Leo O, Carlier Y
J Immunol. 2003 170(8):4237-41.
Post date: 7 years 4 months ago
Amastigote load and cell surface phenotype of infected cells from lesions and lymph nodes of susceptible and resistant mice infected with Leishmania major
Muraille E, De Trez C, Pajak B, Torrentera FA, De Baetselier P, Leo O, Carlier Y
Infect Immun. 2003 71(5):2704-15
Post date: 7 years 4 months ago
Myd88-dependent in vivo maturation of splenic dendritic cells induced by Leishmania donovani and other Leishmania species
De Trez C, Brait M, Leo O, Aebischer T, Torrentera FA, Carlier Y, Muraille E
Infect Immun. 2004 72(2):824-32
Post date: 7 years 4 months ago
iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice
De Trez C, Magez S, Akira S, Ryffel B, Carlier Y, Muraille E
PLoS Pathog. 2009 5(6):e1000494.
Post date: 7 years 4 months ago
Direct visualization of peptide/MHC complexes at the surface and in the intracellular compartments of cells infected in vivo by Leishmania major
Muraille E, Gounon P, Cazareth J, Hoebeke J, Lippuner C, Davalos-Misslitz A, Aebischer T, Muller S, Glaichenhaus N, Mougneau E
PLoS Pathog. 2010 6(10):e1001154.
Post date: 7 years 4 months ago
Toxicity and neuroendocrine regulation of the immune response: a model analysis
Muraille E, Thieffry D, Leo O, Kaufman M
J Theor Biol. 1996 183(3):285-305
Post date: 7 years 4 months ago
Revisiting the Th1/Th2 paradigm
Muraille E, Leo O
Scand J Immunol. 1998 47(1):1-9. Review
Post date: 7 years 4 months ago
Redefining the immune system as a social interface for cooperative processes
Muraille E
Viewed from a neo-Darwinian perspective, the main function of the metazoan immune system (IS) is to insure host integrity against invading microorganisms, which are only considered as selfish competitors that reduce the host's resources, inflict tissue damage, and ultimately compromise host fitness. Coevolution of the host and these competitors has been described as a perpetual arms race (known as the Red Queen hypothesis, Van Valen). This vision implicitly suggests that “The IS evolved under selective pressure imposed by infectious microorganisms" (Janeway) and that the ultimate objective of the IS is to conserve the integrity and sterility of the host. In fact, numerous observations from microbiology and ecology have challenged this paradigm and suggest that infectious organisms and the IS play a crucial, unexpected role in evolution. PLoS Pathog. 2013 9(3):e1003203. Opinion.
Post date: 7 years 4 months ago
Generation of individual diversity: a too neglected fundamental property of adaptive immune system
Muraille E
The fitness gains resulting from development of the adaptive immune system (AIS) during evolution are still the subject of hot debate. A large random repertoire of antigenic receptors is costly to develop and could be the source of autoimmune reactions. And yet, despite their drawbacks, AIS-like systems seem to have been independently acquired in several phyla of metazoans with very different anatomies, longevities, and lifestyles. This article is a speculative attempt to explore the selective pressures, which favored this striking convergent evolution. It is well known that the AIS enables an organism to produce a specific immune response against all natural or artificial antigenic structures. However, it is frequently neglected that this response is highly variable among individuals. In practice, each individual possesses a "private" adaptive immune repertoire. This individualization of immune defenses implies that invasion and escape immune mechanisms developed by pathogens will certainly not always be successful as the specific targets and organization of the immune response are somewhat unpredictable. In a population, where individuals display heterogeneous immune responses to infection, the probability that a pathogen is able to infect all individuals could be reduced compared to a homogeneous population. This suggests that the individual diversity of the immune repertoire is not a by-product of the AIS but of its fundamental properties and could be in part responsible for repeated selection and conservation of the AIS during metazoan evolution. The capacity of the AIS to improve the management of cooperative or parasitic symbiotic relationships at the individual level could be a secondary development due to its progressive integration into the innate immune system. This hypothesis constitutes a new scenario for AIS emergence and explains the selection of MHC restriction and MHC diversification. Front Immunol. 2014 5:208. Opinion.
Post date: 7 years 4 months ago
TH1/TH2 paradigm extended: macrophage polarization as an unappreciated pathogen-driven escape mechanism?
Muraille E, Leo O, Moser M
The classical view of the Th1/Th2 paradigm posits that the pathogen nature, infectious cycle, and persistence represent key parameters controlling the choice of effector mechanisms operating during an immune response. Thus, efficient Th1 responses are triggered by replicating intracellular pathogens, while Th2 responses would control helminth infection and promote tissue repair during the resolution phase of an infectious event. However, this vision does not account for a growing body of data describing how pathogens exploit the polarization of the host immune response to their own benefit. Recently, the study of macrophages has illustrated a novel aspect of this arm race between pathogens and the immune system, and the central role of macrophages in homeostasis, repair and defense of all tissues is now fully appreciated. Like T lymphocytes, macrophages differentiate into distinct effectors including classically (M1) and alternatively (M2) activated macrophages. Interestingly, in addition to represent immune effectors, M1/M2 cells have been shown to represent potential reservoir cells to a wide range of intracellular pathogens. Subversion of macrophage cell metabolism by microbes appears as a recently uncovered immune escape strategy. Upon infection, several microbial agents have been shown to activate host metabolic pathways leading to the production of nutrients necessary to their long-term persistence in host. The purpose of this review is to summarize and discuss the strategies employed by pathogens to manipulate macrophage differentiation, and in particular their basic cell metabolism, to favor their own growth while avoiding immune control. Front Immunol. 2014 5:603. Review.
Post date: 7 years 4 months ago
The Unspecific Side of Acquired Immunity Against Infectious Disease: Causes and Consequences
Muraille E
Acquired immunity against infectious disease (AIID) has long been considered as strictly dependent on the B and T lymphocytes of the adaptive immune system. Consequently, AIID has been viewed as highly specific to the antigens expressed by pathogens. However, a growing body of data motivates revision of this central paradigm of immunology. Unrelated past infection, vaccination, and chronic infection have been found to induce cross-protection against numerous pathogens. These observations can be partially explained by the poly-specificity of antigenic T and B receptors, the Mackaness effect and trained immunity. In addition, numerous studies highlight the importance of microbiota composition on resistance to infectious disease via direct competition or modulation of the immune response. All of these data support the idea that a non-negligible part of AIID in nature can be nonspecific to the pathogens encountered and even of the antigens expressed by pathogens. As this protection may be dependent on the private T and B repertoires produced by the random rearrangement of genes, past immune history, chronic infection, and microbiota composition, it is largely unpredictable at the individual level. However, we can reasonably expect that a better understanding of the underlying mechanisms will allow us to statistically predict cross-protection at the population level. From an evolutionary perspective, selection of immune mechanisms allowing for partially nonspecific AIID would appear to be advantageous against highly polymorphic and rapidly evolving pathogens. This new emerging paradigm may have several important consequences on our understanding of individual infectious disease susceptibility and our conception of tolerance, vaccination and therapeutic strategies against infection and cancer. It also underscores the importance of viewing the microbiota and persisting infectious agents as integral parts of the immune system. Front Microbiol. 2016 6:1525. Review.
Post date: 7 years 4 months ago
MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection
Copin R, De Baetselier P, Carlier Y, Letesson JJ, Muraille E
IFN-gamma is a key cytokine controlling Brucella infection. One of its major function is the stimulation of Brucella-killing effector mechanisms, such as inducible NO synthase (iNOS)/NOS2 activity, in phagocytic cells. In this study, an attempt to identify the main cellular components of the immune response induced by Brucella melitensis in vivo is made. IFN-gamma and iNOS protein were analyzed intracellularly using flow cytometry in chronically infected mice. Although TCRbeta(+)CD4(+) cells were the predominant source of IFN-gamma in the spleen, we also identified CD11b(+)LY-6C(+)LY-6G(-)MHC-II(+) cells as the main iNOS-producing cells in the spleen and the peritoneal cavity. These cells appear similar to inflammatory dendritic cells recently described in the mouse model of Listeria monocytogenes infection and human psoriasis: the TNF/iNOS-producing dendritic cells. Using genetically deficient mice, we demonstrated that the induction of iNOS and IFN-gamma-producing cells due to Brucella infection required TLR4 and TLR9 stimulation coupled to Myd88-dependent signaling pathways. The unique role of MyD88 was confirmed by the lack of impact of Toll-IL-1R domain-containing adaptor inducing IFN-beta deficiency. The reduction of IFN-gamma(+) and iNOS(+) cell frequency observed in MyD88-, TLR4-, and TLR9-deficient mice correlated with a proportional lack of Brucella growth control. Taken together, our results provide new insight into how immune responses fight Brucella infection. J Immunol. 2007 178(8):5182-91
Post date: 7 years 4 months ago
In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice
Copin R, Vitry MA, Hanot Mambres D, Machelart A, De Trez C, Vanderwinden JM, Magez S, Akira S, Ryffel B, Carlier Y, Letesson JJ, Muraille E
Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b⁺ F4/80⁺ MHC-II⁺ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS⁺ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis. PLoS Pathog. 2012;8(3):e1002575.
Post date: 7 years 4 months ago
Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of Brucella melitensis infection in mice
Vitry MA, De Trez C, Goriely S, Dumoutier L, Akira S, Ryffel B, Carlier Y, Letesson JJ, Muraille E
Brucella spp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control of Brucella infection. The importance of lymphocyte subsets in the control of Brucella growth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control of Brucella melitensis 16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4(+) T cells in the control of B. melitensis infection, whereas IFN-γ-producing CD8(+) T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course of B. melitensis infection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis. Infect Immun. 2012 80(12):4271-80
Post date: 7 years 4 months ago
Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis
Vitry MA, Hanot Mambres D, De Trez C, Akira S, Ryffel B, Letesson JJ, Muraille E
Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase-mediated isotype switch. In striking contrast, the presence of memory IFN-γ-producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis. J Immunol. 2014 192(8):3740-52
Post date: 7 years 4 months ago
Brucella melitensis invades murine erythrocytes during infection
Vitry MA, Hanot Mambres D, Deghelt M, Hack K, Machelart A, Lhomme F, Vanderwinden JM, Vermeersch M, De Trez C, Pérez-Morga D, Letesson JJ, Muraille E
Brucella spp. are facultative intracellular Gram-negative coccobacilli responsible for brucellosis, a worldwide zoonosis. We observed that Brucella melitensis is able to persist for several weeks in the blood of intraperitoneally infected mice and that transferred blood at any time point tested is able to induce infection in naive recipient mice. Bacterial persistence in the blood is dramatically impaired by specific antibodies induced following Brucella vaccination. In contrast to Bartonella, the type IV secretion system and flagellar expression are not critically required for the persistence of Brucella in blood. ImageStream analysis of blood cells showed that following a brief extracellular phase, Brucella is associated mainly with the erythrocytes. Examination by confocal microscopy and transmission electron microscopy formally demonstrated that B. melitensis is able to invade erythrocytes in vivo. The bacteria do not seem to multiply in erythrocytes and are found free in the cytoplasm. Our results open up new areas for investigation and should serve in the development of novel strategies for the treatment or prophylaxis of brucellosis. Invasion of erythrocytes could potentially protect the bacterial cells from the host's immune response and hamper antibiotic treatment and suggests possible Brucella transmission by bloodsucking insects in nature. Infect Immun. 2014 82(9):3927-38
Post date: 7 years 4 months ago
In Situ Characterization of Splenic Brucella melitensis Reservoir Cells during the Chronic Phase of Infection in Susceptible Mice
Hanot Mambres D, Machelart A, Vanderwinden JM, De Trez C, Ryffel B, Letesson JJ, Muraille E
Brucella are facultative intracellular Gram-negative coccobacilli that chronically infect humans as well as domestic and wild-type mammals, and cause brucellosis. Alternatively activated macrophages (M2a) induced by IL-4/IL-13 via STAT6 signaling pathways have been frequently described as a favorable niche for long-term persistence of intracellular pathogens. Based on the observation that M2a-like macrophages are induced in the spleen during the chronic phase of B. abortus infection in mice and are strongly infected in vitro, it has been suggested that M2a macrophages could be a potential in vivo niche for Brucella. In order to test this hypothesis, we used a model in which infected cells can be observed directly in situ and where the differentiation of M2a macrophages is favored by the absence of an IL-12-dependent Th1 response. We performed an in situ analysis by fluorescent microscopy of the phenotype of B. melitensis infected spleen cells from intranasally infected IL-12p40-/- BALB/c mice and the impact of STAT6 deficiency on this phenotype. Most of the infected spleen cells contained high levels of lipids and expressed CD11c and CD205 dendritic cell markers and Arginase1, but were negative for the M2a markers Fizz1 or CD301. Furthermore, STAT6 deficiency had no effect on bacterial growth or the reservoir cell phenotype in vivo, leading us to conclude that, in our model, the infected cells were not Th2-induced M2a macrophages. This characterization of B. melitensis reservoir cells could provide a better understanding of Brucella persistence in the host and lead to the design of more efficient therapeutic strategies. PLoS One. 2015 10(9):e0137835.
Post date: 7 years 4 months ago
Identification of immune effectors essential to the control of primary and secondary intranasal infection with Brucella melitensis in mice
Hanot Mambres D, Machelart A, Potemberg G, De Trez C, Ryffel B, Letesson JJ, Muraille E
The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35(-/-) mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35- and IL-17A-dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4(+) and CD8(+) α/β(+) T cells are sufficient to mount a protective immune response and that an IL-17A-mediated response can compensate for the partial deficiency of an IFN-γ-mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ-and IL-17RA-mediated responses in the control of mucosal infection by Brucella. J Immunol. 2016 196(9):3780-93
Post date: 7 years 4 months ago
L'excellence scientifique en question
Eric Muraille
La vision occidentale du monde, notre construction de la réalité, une grande part des aspects tant matériels que sociaux de la vie moderne découlent de la recherche scientique. De nombreuses études lient la prospérité des nations à leur productivité scientique, faisant de la recherche scientique l’un des moteurs de la croissance économique. Pourtant, la méthodologie et l’organisation de la recherche scientique restent peu connues des citoyens. Le mythe d’individus isolés, subissant de brèves illuminations,tels Archimède et son bain, Newton et sa pomme, persiste dans l’imaginaire collectif. Cet article présente les principaux acteurs de la recherche scientique et questionne le choix des critères de son financement actuellement en vigueur. Il analyse l’impact de ces critères sur son organisation dans les universités et les services que la recherche fournit à la société. La recherche en Fédération Wallonie-Bruxelles (FW-B), en Belgique, est prise en exemple. Revue des Questions Scientifiques, 2016, 187(4): 529-548
Post date: 7 years 4 months ago
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