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Immune Detection and Elimination of Pathogens

Etienne Meunier

Group Leader

The team “Immune detection and elimination of pathogens” has been launched thanks to the “Fondation pour la Recherche Médicale” (FRM) program “Amorçage Jeunes Equipes” and the ATIP-AVENIR program for young investigators granted by CNRS-INSERM’.

 

 

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Cell autonomous immunity constitutes a common immunity among all the species from the Life kingdom by fighting any kind of threat that could prevent cells from carrying out the essential processes of life (protein, lipid or nucleic acid production).

Although being highly efficient at eliminating microorganisms that are not adapted to the intracellular compartment, successful intracellular microorganism such as Mycobacterium tuberculosis or Francisella tularensis bacteria can survive and even proliferate into the cells. Why our cell autonomous immunity, a process extremely strong and microbicidal is not able to efficiently kill and eliminate these bacteria is one of the questions we aim at answering.

 

One lead consists at studying the Interferons-induced effectors, more than 2000, as the Interferons, host proteins, were shown to grant the cells with new and stronger cell-autonomous mechanisms, hence helping bacterial killing and elimination. Based on the fact that the immune system has co-evolved with pathogenic bacteria and had to develop strategies to protect the host, the long term goal is to help at new therapeutics axis based on host immune system modulation during infections.

 

Research projects

To unlock the immune response: The cellular and molecular means by which intracellular sensors detect the pathogens

To communicate: Novel alarmin discovery and involvement in microbial elimination

To bypass the intracellular PRRs: Non-canonical functions of cytosolic sensors

The Stromal immunity: The immune and microbicidal responses of the epithelia

Main Publications

Meunier E and Broz, P. (2016) Interferon-inducible GTPases in cell autonomous and innate immunity. Cell Microbiol 18: 168–180


Meunier E et al. (2015) Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nat Immunol 16: 476–484


Meunier E et al. (2014) Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature 509: 366–370


Lefèvre L 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 38: 1038–1049


Meunier E et al. (2012) Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation. Nanomedicine: NBM 8: 987–995

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Murine macrophage infected with Francisella novicida (Red) and stained for LC3 (Green).

 

Scientists

Etienne Meunier

CNRS Research associate in immunology
Céline Cougoule

Céline Cougoule

CNRS Research associate

Research Assistant

Pierre-Jean Bordignon

Pierre-Jean Bordignon

Fixed-term CNRS Assistant Researcher

Post-Doctoral Fellows

Elif Eren

Fondation pour la Recherche Médicale post-doctoral fellow
Rémi Planès

Rémi Planès

ATIP-Avenir post-doctoral fellow

PhD Student

Salimata Bagayoko

Fellow of French-Mali embassy

Collaborations :

Olivier Neyrolles, IPBS institute, Toulouse, France

Julien Buyck: Univ. of Poitiers, France

Jessica Quintin: Pasteur Institute, Paris, France

Patrizia D’Adamo, San Rafaele institute, Milan, Italy

Petr Broz, Univ. of Lausanne, Lausanne, Switzerland

Dr Peter J. Peters, Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht, Netherlands

Dr Hans Clevers, Hubrecht Institute, Utrecht, Netherlands

Funding : 

The team is supported by several grants and funding from:

Fondation pour la Recherche Médicale (2016-2019), program « amorçage jeunes équipes »

ATIP-Avenir (2017-2020), young team leader program

ERC Starting Grant (2019-2023) from the EU

Agence Nationale pour la Recherche (2019-2022)

University of Toulouse

Fondation Fonroga

Partnership Hubert Curien (PHC) VAN GOGH 2018

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  • Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells. Cougoule C, Lastrucci C, Guiet R, Mascarau R, Meunier E, Lugo-Villarino G, Neyrolles O, Poincloux R, Maridonneau-Parini I. Front Immunol. 2018 Apr 30;9:846. doi: 10.3389/fimmu.2018.00846. eCollection 2018
  • LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation. Santos JC, Dick MS, Lagrange B, Degrandi D, Pfeffer K, Yamamoto M, Meunier E, Pelczar P, Henry T, Broz P. EMBO J. 2018 Mar 15;37(6). pii: e98089. doi: 10.15252/embj.201798089. Epub 2018 Feb 19.
  • Impaired phagocytosis directs human monocyte activation in response to fungal derived β-glucan particles. Camilli G, Eren E, Williams DL, Aimanianda V, Meunier E, Quintin J. Eur J Immunol. 2018 May;48(5):757-770. doi: 10.1002/eji.201747224. Epub 2018 Feb 5.
  • The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity. Schneider KS, Groß CJ, Dreier RF, Saller BS, Mishra R, Gorka O, Heilig R, Meunier E, Dick MS, Ćiković T, Sodenkamp J, Médard G, Naumann R, Ruland J, Kuster B, Broz P, Groß O. Cell Rep. 2017 Dec 26;21(13):3846-3859. doi: 10.1016/j.celrep.2017.12.018.
  • The Gasdermin-D pore acts as a conduit for IL-1β secretion in mice. Heilig R, Dick MS, Sborgi L, Meunier E, Hiller S, Broz P. Eur J Immunol. 2018 Apr;48(4):584-592. doi: 10.1002/eji.201747404. Epub 2018 Jan 15.
  • IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection. Wallet P, Benaoudia S, Mosnier A, Lagrange B, Martin A, Lindgren H, Golovliov I, Michal F, Basso P, Djebali S, Provost A, Allatif O, Meunier E, Broz P, Yamamoto M, Py BF, Faudry E, Sjöstedt A, Henry T. PLoS Pathog. 2017 Oct 2;13(10):e1006630. doi: 10.1371/journal.ppat.1006630. eCollection 2017 Oct.
  • Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response. Alonso H, Parra J, Malaga W, Payros D, Liu CF, Berrone C, Robert C, Meunier E, Burlet-Schiltz O, Rivière M, Guilhot C. Sci Rep. 2017 Aug 11;7(1):7913. doi: 10.1038/s41598-017-08489-7.
  • Evolutionary Convergence and Divergence in NLR Function and Structure. Meunier E, Broz P. Trends Immunol. 2017 Oct;38(10):744-757. doi: 10.1016/j.it.2017.04.005. Epub 2017 May 31. Review.
  • Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice. Drougard A, Fournel A, Marlin A, Meunier E, Abot A, Bautzova T, Duparc T, Louche K, Batut A, Lucas A, Le-Gonidec S, Lesage J, Fioramonti X, Moro C, Valet P, Cani PD, Knauf C. Sci Rep. 2016 Aug 23;6:31849. doi: 10.1038/srep31849.
  • Interferon-inducible GTPases in cell autonomous and innate immunity. Meunier E, Broz P. Cell Microbiol. 2016 Feb;18(2):168-80. doi: 10.1111/cmi.12546. Epub 2015 Dec 28. Review.
  • Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization. Meunier E, Broz P. J Vis Exp. 2015 Jul 28;(101):e52960. doi: 10.3791/52960.
  • LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis. Lefèvre L, Authier H, Stein S, Majorel C, Couderc B, Dardenne C, Eddine MA, Meunier E, Bernad J, Valentin A, Pipy B, Schoonjans K, Coste A. Nat Commun. 2015 Apr 15;6:6801. doi: 10.1038/ncomms7801.
  • Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Meunier E, Wallet P, Dreier RF, Costanzo S, Anton L, Rühl S, Dussurgey S, Dick MS, Kistner A, Rigard M, Degrandi D, Pfeffer K, Yamamoto M, Henry T, Broz P. Nat Immunol. 2015 May;16(5):476-484. doi: 10.1038/ni.3119. Epub 2015 Mar 16.
  • Interferon-induced guanylate-binding proteins promote cytosolic lipopolysaccharide detection by caspase-11. Meunier E, Broz P. DNA Cell Biol. 2015 Jan;34(1):1-5. doi: 10.1089/dna.2014.2701. Review.
  • Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Meunier E, Dick MS, Dreier RF, Schürmann N, Kenzelmann Broz D, Warming S, Roose-Girma M, Bumann D, Kayagaki N, Takeda K, Yamamoto M, Broz P. Nature. 2014 May 15;509(7500):366-70. doi: 10.1038/nature13157. Epub 2014 Apr 16.
  • Targeting a G-protein-coupled receptor overexpressed in endocrine tumors by magnetic nanoparticles to induce cell death. Sanchez C, El Hajj Diab D, Connord V, Clerc P, Meunier E, Pipy B, Payré B, Tan RP, Gougeon M, Carrey J, Gigoux V, Fourmy D. ACS Nano. 2014 Feb 25;8(2):1350-63. doi: 10.1021/nn404954s. Epub 2014 Jan 14.
  • The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum. Lefèvre L, Lugo-Villarino G, Meunier E, Valentin A, Olagnier D, Authier H, Duval C, Dardenne C, Bernad J, Lemesre JL, Auwerx J, Neyrolles O, Pipy B, Coste A. Immunity. 2013 May 23;38(5):1038-49. doi: 10.1016/j.immuni.2013.04.010. Epub 2013 May 16.
  • Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation. Meunier E, Coste A, Olagnier D, Authier H, Lefèvre L, Dardenne C, Bernad J, Béraud M, Flahaut E, Pipy B. Nanomedicine. 2012 Aug;8(6):987-95. doi: 10.1016/j.nano.2011.11.004. Epub 2011 Nov 16.
  • Nrf2, a PPARγ alternative pathway to promote CD36 expression on inflammatory macrophages: implication for malaria. Olagnier D, Lavergne RA, Meunier E, Lefèvre L, Dardenne C, Aubouy A, Benoit-Vical F, Ryffel B, Coste A, Berry A, Pipy B. PLoS Pathog. 2011 Sep;7(9):e1002254. doi: 10.1371/journal.ppat.1002254. Epub 2011 Sep 15.
  • Frustrated phagocytosis on micro-patterned immune complexes to characterize lysosome movements in live macrophages. Labrousse AM, Meunier E, Record J, Labernadie A, Beduer A, Vieu C, Ben Safta T, Maridonneau-Parini I. Front Immunol. 2011 Oct 12;2:51. doi: 10.3389/fimmu.2011.00051. eCollection 2011.