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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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Inflammasomes are intracellular multi-protein complexes that play essential functions in immunity against microbial pathogens. Upon microbial sensing, inflammasomes induce protease caspase-1-dependent maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as gasdermin-D-dependent cell necrosis, called pyroptosis. While both pyroptosis and IL-1β/IL-18 release play key parts in controlling microbial infections, the host-regulated pathways that promote detection of microbial ligands by cytosolic inflammasome-forming sensors and the non-canonical functions of inflammasome-derived components, remain to be fully characterized.

Building on my expertise in the field of inflammasome regulators during microbial infections, my group aims at answering one major question:
What makes that the innate immune system confers host protection, and why does such fantastic machinery can fail to?

 

To address this question, we use a combination of state-of-the-art and innovative technologies in biochemistry, molecular and cell biology, and immunology in various in vitro and in vivo models. For example, we are developing an unbiased genome-wide search for novel effectors involved in inflammasome activation based on the unprecedented coupling of the CRISPR-Cas9 technology to automated visual high-throughput screening. Therefore, this multidisciplinary research program aims at providing breakthroughs in the field of microbial pathogens detection by the host immune system, and to nucleate entirely novel immune paradigms on microbial sensing by new unsuspected host cytosolic proteins, namely the gasdermins.

  1. To unlock the immune response: The cellular and molecular means by which intracellular sensors detect pathogens
  2. To shortcut the intracellular PRRs: Non-canonical functions of cytosolic-derived sensors
  3. The Stromal immunity: To decipher 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 Engineer

Audrey Hessel

fixed-term CNRS Engineer

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

Stephen Adonaí León Icaza

CIENCIAMED scholarship

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:

- ERC Starting Grant (2019-2023) from the EU

- Agence Nationale pour la Recherche (2019-2022)

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

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

 

- 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.