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Interactions des mycobactéries avec les cellules-hôte

Olivier Neyrolles

Responsable d'équipe

Le but principal de notre groupe de recherche est de mieux comprendre les interactions hôte-pathogène dans la tuberculose aux niveaux moléculaire et cellulaire, de la découverte de nouveaux gènes de virulence dans Mycobacterium tuberculosis à l'identification des mécanismes immunitaires impliqués dans la défense de l'hôte contre le pathogène, avec l'objectif global de proposer de meilleures stratégies pour contrôler la maladie.

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Notre recherche vise à explorer les liens entre la physiologie mycobactérienne et la virulence, et entre le métabolisme des cellules-hôtes et l'immunité à M. tuberculosis dans le contexte de la tuberculose et des co-infections tuberculeuses (par exemple le VIH) en utilisant une combinaison d'approches globales 'omics' et d'études basées sur des candidats, de la molécule unique à l'échelle de l'organisme entier.

Notre équipe est hautement interdisciplinaire, impliquant des scientifiques et des professeurs de biochimie, de génétique microbienne et d'immunologie, et travaille en étroite collaboration avec d'autres laboratoires du monde entier dans le cadre de plusieurs réseaux nationaux et internationaux soutenus par des organismes de financement nationaux (ex. Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation Bettencourt-Schueller) et internationaux (ex. programme Horizon 2020 de l'Union Européenne)

Our Research topic on "The Mononuclear Phagocyte System in Infectious Disease" is now published in Frontiers in Immunology!

This editorial project led by junior scientists of the TB & Infection Biology Department, including Drs. G. Lugo-Villarino, C. Cougoule, C. Vérollet, E. Meunier and Y. Rombouts, is now published in Frontiers in Immunology. The topic contains contributions by world class leaders in the field, including Drs. S. Gordon, T. Sparwasser, T. Soldati, P. Peters, D. Russell, J.P. Gorvel and many others, and is a platform for discussion and debate about relevant issues and themes in this field. Recent progress, critical knowledge gaps, and conceptual frameworks for future MPS investigation in the context of infectious disease are discussed by expert junior and senior scientists.

Read the Topic content here...

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To follow the MOOC on Tuberculosis, click here...

The MOOC took place between Januay 29 and April 02 2018.

Selection de publications

  • Levillain, Poquet et al. (2017) Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation. PLOS Pathog
  • Bénard et al. (2017) B cells producing type I interferon modulate macrophage polarization in tuberculosis. Am J Respir Crit Care Med
  • Troegeler et al. (2017) C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. Proc Natl Acad Sci USA
  • Lastrucci et al. (2015) Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis. Cell Research
  • Gouzy et al. (2013) Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate. Nature Chem Biol

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L'aspartate atteint le phagosome mycobactérien dans les macrophages infectés et sert de source d'azote pour le pathogène. Des bactéries marquées au 13C ont été utilisées pour infecter les macrophages de souris. Après avoir soumis les cellules à de l'aspartate 15N, les compositions isotopiques de 13C et de 15N ont été analysées par NanoSIMS. Les images montrent une cellule  représentative infectée. A gauche, l'image enregistrée du 12C14N  montrant l'aspect histologique de la cellule. Au milieu, la carte des fractions atomiques du 13C (en %) de la zone correspondante. A droite, l'image du rapport 15N/14N, indiquant l'absorption de 15N-aspartate. Pour une meilleure visibilité, le ratio a été multiplié par 10 000. Le rapport 15N/14N à l'abondance naturelle 15N apparaît en bleu.

 

Suivez nous sur Twitter (@ONeyrolles)

Selected publications

This is short list of our main recent contributions to mycobacterial research. Other papers and reviews are available through Pubmed

 

Our latest reviews on TB vaccine research, illustrating our contribution to the TBVAC2020 consortium

Voss et al. 2018. Progress and challenges in TB vaccine development F1000Res

 

Kaufmann et al. 2017. TBVAC2020: Advancing tuberculosis vaccines from discovery to clinical development Front Immunol

 

Innate immunity to mycobacteria and other pathogens

Lugo-Villarino et al. 2018. The C-type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis Front Immunol

 

Bénard et al. 2017. B cells producing type I interferon modulate macrophage polarization in tuberculosis Am J Respir Crit Care Med

 

Troegeler et al. 2017. C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon  signaling in dendritic cells Proc Natl Acad Sci USA

 

Lastrucci et al. 2015. Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis Cell Research

 

Lugo-Villarino G & O Neyrolles. 2014. Manipulation of the mononuclear phagocyte system by Mycobacterium tuberculosis Cold Spring Harb Perspect Med

 

Troegeler A et al. 2014. An efficient siRNA-mediated gene silencing in primary human monocytes, dendritic cells and macrophages Immunol Cell Biol

 

Lefèvre L*, Lugo-Villarino G* et al. 2013. The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum Immunity

 

Tanne A et al. 2009. A murine DC-SIGN homolog contributes to early host defense against Mycobacterium tuberculosis J Exp Med

 

Tailleux L et al. 2005. DC-SIGN induction in alveolar macrophages defines a privileged target host cell population for mycobacteria in patients with tuberculosis PLOS Med

 

Tailleux L et al. 2003. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells J Exp Med

 

Maeda N et al. 2003. The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan J Biol Chem

Mycobacterial evolution, physiology and virulence

Levillain F et al. 2017. Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation PLOS Pathog

 

Neyrolles O et al. 2015. Mycobacteria, metals, and the macrophage Immunol Rev

 

Gouzy A et al. 2014. Nitrogen metabolism in Mycobacterium tuberculosis physiology and virulence Nat Rev Microbiol

 

Gouzy A et al. 2014. Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection PLOS Pathog

 

Gouzy A et al. 2013. Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate Nat Chem Biol

 

Soldati T & O Neyrolles. 2012. Mycobacteria and the intraphagosomal environment: take it with a pinch of salt(s)! Traffic

 

Botella H et al. 2012. Metallobiology of host-pathogen interactions: an intoxicating new insight Trends Microbiol

 

Botella H et al. 2011. Mycobacterial P1-type ATPases mediate resistance to zinc poisoning in human macrophages Cell Host Microbe

 

Brodin P et al. 2010. High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling PLOS Pathog

 

Becq J et al. 2007. Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli Mol Biol Evol

 

Rosas-Magallanes V et al. 2006. Horizontal transfer of a virulence operon to the ancestor of Mycobacterium tuberculosis Mol Biol Evol

 

A funny paper you may want to read...

Neyrolles O et al. 2006. Is adipose tissue a place for Mycobacterium tuberculosis persistence? PLOS ONE

 

Collaborations

Nous sommes redevables à nos nombreux collaborateurs nationaux et internationaux, y compris :

 

  • Priscille Brodin Centre d'Infection et d'Immunité de Lille, France
  • Philippe Langela, Muriel Thomas & Luis Bermudez INRA, Jouy en Josas, France
  • Patrice Catty Commissariat à l’Energie Atomique, Grenoble, France
  • Brigitte Gicquel, Ludovic Tailleux, Roland Brosch & Lluis Quintana-Murci Institut Pasteur, Paris
  • Axel Magalon Laboratory of bacterial chemistry, Marseille
  • Simon Fillatreau DRFZ, Berlin, Germany & INEM, Paris, France
  • Annabel Parret & Matthias Willmans EMBL-Centre for Cellular and Molecular Imaging, Hamburg, Germany
  • Manfred Wuhrer Leiden University Medical Centre, Leiden, The Netherlands
  • Frank Verreck Biomedical Primate Research Centre Rijswijk, The Netherlands
  • Bernd Lepenies University of Veterinary Medicine, Hannover, Germany
  • Luciana Balboa & Maria Carmen Sasiain Academia Nacional de Medicina, Buenos Aires, Argentina
  • Sabine Ehrt & Dirk Schnappinger Weill Cornell Medical College, NY, USA
  • Luiz Pedro de Carvalho The Francis Crick Institute, London, UK
  • Gerald Larrouy-Maumus Imperial College, London, UK
  • Elsa Anes University of Lisbon, Portugal

Financements:

Notre équipe est soutenue par plusieurs subventions et bourses d'études :

  • European Union (FP7 & H2020)
  • Agence Nationale de la Recherche
  • Fondation pour la Recherche Médicale
  • Agence nationale de recherche sur le sida et les hépatites virales
  • Fondation ARC pour la recherche sur le cancer
  • Vaincre la Mucoviscidose
  • Association Gregory Lemarchal
  • Fondation Mérieux
  • Fondation Bettencourt-Schueller
  • ECOS-Sud exchange programme (Argentina)
  • European Respiratory Society

 

Notre équipe est officiellement labellisée par Fondation pour la Recherche Médicale (2016-2019)

 

Prix

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December 2017 - Anthony Troegeler is awarded the Bretesche Prize in medicine from the Toulouse Academy of sciences. 

Anthony did his PhD studies in our lab where he worked on the role of the innate immune receptor DCIR in immunity to tuberculosis. His work was published in January 2017 in Proc Natl Acad Sci USA. He will receive the Prize on December 3 at the Hôtel d'Assézat, Toulouse.

June 2017 - Yoann Rombouts is awarded the IGO Young Glycoscientist Award 2017. Read more

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Dec 2016 - Olivier Neyrolles receives the Sanofi-Institut Pasteur National Junior Award in the field of neglected tropical diseases for his research into tuberculosis, during a ceremony at the Institut Pasteur, Paris. Olivier and his team contributed to understading several aspects of the complex interactions between the tuberculosis bacillus,Mycobacterium tuberculosis, and its host, including anti-mycobacterial immunity and mycobacterial evolution, physiology and virulence... Read more

 

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Dec 2014 - Alexandre Gouzy receives the Sanofi 2014 Prize from the Toulouse Academy of Sciences

Read more

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Feb 2014 - Olivier Neyrolles receives the "Coup d’élan pour la Recherche Française" Prize from the Bettencourt Schueller Foundation during a ceremony at the Institut de France, Paris, in which Madame F. Bettencourt Meyers presented the Prize. This Prize rewards teams specifically chosen for the promising nature of their research programs. The Prize recognises both the quality of the work of Olivier Neyrolles’ team and the quality of the research conducted in the Tuberculosis & Infection Biology Department at IPBS in the field of vaccine and antibiotics development.

 

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April 2012 - Helene Botella, winner of the AXA-Academy of Sciences prize based on her work in the involvement of zinc as a natural mechanism to fight against infections Read more 

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2009 - Olivier Neyrolles receives the CNRS Bronze medal Read more

 

 

Nous sommes extrêmement fiers de nos anciens assistants de recherche, doctorants et post-doctorants qui poursuivent maintenant leur carrière dans les meilleurs laboratoires et entreprises en sciences de la vie !

 

  • Karine Pingris Research assistant, Evotec, Toulouse
  • André Colom Research assistant, Evotec, Toulouse
  • Danilo Pietretti Post-doctoral fellow, Wageningen University, The Netherlands
  • Alan Bénard Post-doctoral fellow, University Hospital, Erlangen, Germany
  • Anthony Troegeler Pierre Fabre, Toulouse
  • Anna Grabowska Research associate, London School of Hygiene & tropical Medicine, London, UK
  • Kanjana Nukdee Professor, Ubon Ratchathani University, Thailand
  • Ingrid Mercier Infotel, Toulouse, France
  • Alexandre Gouzy Post-doctoral fellow, Weill Cornell Medical College, NY, USA
  • Hélène Botella Post-doctoral fellow, Weill Cornell Medical College, NY, USA
  • Antoine Tanne Project manager, Agenus, Boston, USA
  • Jichan Jang Professor, Gyeongsang National University, Jinju, South Korea
  • Chongzhen Wang Associate professor, Guilin Medical College, Guilin, China
  • Chuan Wang Lecturer, School of basic medical science, Fudan University, Shanghai, China