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Mycobacterial Interactions with Host Cells

Olivier Neyrolles

Group Leader

The main goal of our research group is to better understand host-pathogen interactions in TB on the molecular and cellular levels, from the discovery of novel virulence genes in Mycobacterium tuberculosis to the identification of immune mechanisms involved in host defense against the pathogen, with the overall objective of proposing better strategies to control disease.

 

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Our research aims at exploring the links between mycobacterial evolution, physiology and virulence, and between host cell metabolism and immunity to M. tuberculosis in the context of TB and TB co-infections (e.g. HIV) using a combination of global ‘omics’ approaches and candidate-based studies, from the single molecule to the whole organism level.

Our team is highly interdisciplinary, involving scientists and professors in biochemistry, microbial genetics and immunology, and works in close collaboration with other laboratories worldwide in the context of several national and international networks supported by national (e.g. Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation Bettencourt-Schueller) and international (e.g. European Union H2020 program) funding bodies.

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.

Selected publications

  • Souriant et al. (2019) Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages. Cell Rep
  • Freire*, Gutierrez* et al. (2019) An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death. Mol Cell
  • 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

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MbcT toxin induces death of Mycobacterium tuberculosis. 
When the MbcT toxin is produced in the absence of its antidote, it kills the bacteria (shown in red).
© Antonio Peixoto, Claude Gutierrez, and Olivier Neyrolles | IPBS | CNRS/UPS

 

 

Follow us on 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 G et al. 2018. Progress and challenges in TB vaccine development F1000Res

 

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

 

Scriba T et al. 2016. Vaccination against tuberculosis with whole-cell mycobacterial vaccines J Infect Dis

 

Innate immunity to mycobacteria and other pathogens

Souriant et al. 2019. Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages Cell Rep

 

Dumas A et al. 2018. The host microbiota contributes to early protection against lung colonization by Mycobacterium tuberculosis Front Immunol

 

Lugo-Villarino G 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 A et al. 2017. B cells producing type I interferon modulate macrophage polarization in tuberculosis Am J Respir Crit Care Med

 

Troegeler A 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 C  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

Freire*, Gutierrez* et al. 2019. An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death Mol Cell

 

Levillain F*, Poquet Y* 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

 

Rodriguez GM & O Neyrolles. 2013. Metallobiology of tuberculosis Microbiol Spectr

 

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*, Poquet Y*, Levillain*, Peguillet I* 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

We are indebtful to our many national and international collaborators, including:

 

  • 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, Pierre Charneau & Lluis Quintana-Murci Institut Pasteur, Paris
  • Axel Magalon Laboratory of bacterial chemistry, Marseille
  • Simon Fillatreau 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
  • 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

Funding

Our team is supported by several grants and fellowships from:

  • European Union (FP7 & H2020)
  • ERA-NET JPI-AMR
  • MSDAvenir
  • 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

 

Our team is officially labelled by the Fondation pour la Recherche Médicale (2016-2019)

 

Prizes

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October 2018 - The 2018 PEPS Prize for Pedagogical Innovation is awarded to the IMMUNOVA project (Active, interactive and flexible learning in immunology) led by Prof. Denis Hudrisier.

The IMMUNOVA project is composed of two axes: the first is the strong use of digital resources allowing the students to prepare themselves before and after the face-to-face sessions (also available online), which provides greater flexibility and learning autonomy for all students, especially those who cannot attend classes according to established schedules; for the second axis, the students are offered to conduct team projects in immunology according to different approaches (e.g., digital resource generation, interviews with researchers, 3D printing of proteins in FabLabs, conception of serious games).

Known more about the project – Watch the video!

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

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Dec 2016 - Dr. 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 - Dr. Alexandre Gouzy receives the Sanofi 2014 Prize from the Toulouse Academy of Sciences

Read more

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Feb 2014 - Dr. 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 - Dr. 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 - Dr. Olivier Neyrolles receives the CNRS Bronze medal Read more

 

 

We are extremely proud of our former research assistants, PhD students and post-doctoral fellows who are now continuing their career in the best labs, enterprises and institutions in life sciences!

 

  • Alexia Dumas
  • Karine Pingris Research assistant, Evotec, Toulouse
  • André Colom Research assistant, Evotec, Toulouse
  • Danilo Pietretti Consultant Animal Health at the Food and Agriculture Organization of the United Nations, Rome, Italy
  • Alan Bénard Post-doctoral fellow, University Hospital, Erlangen, Germany
  • Anthony Troegeler Scientific Attaché, UDEAR, 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