Henry T - I2BA

The main model used in the lab to study antibacterial innate immune responses is the zoonotic bacterium Francisella novicida. This bacterium closely related to Francisella tularensis, the agent of tularemia replicates to very high number in the cytosol of macrophages and is thus a fantastic model to study cytosolic immune responses. The team study how macrophages detect invasion in the cytosol and mount an immune response. We also study how inflammasome activation is regulated by Guanylate Binding proteins (GBPs) and eicosanoids.

Francisella is a highly virulent pathogen. The team also study Francisella virulence factors and especially the type VI secretion system (T6SS), which is critical for virulence, bacterial escape into the cytosol and activation of the cytosolic immune responses including the inflammasome.

The pathological activation of inflammasomes is mainly studied in the autoinflammatory diseases linked to mutation in the MEFV gene encoding the pyrin inflammasome sensor. The most frequent pyrin-associated autoinflammatory disease is the Familial Mediterranean Fever. From the fundamental study of pyrin inflammasome mechanism, we aim at understanding the pyrin-associated diseases and develop novel therapeutic and diagnostic strategies.

Recently, we have also developed novel lines of research on ALPK1 and the associated auto-inflammatory ROSAH syndrome.

Our team belongs to the CeRéMAIA, the national reference center for autoinflammatory diseases and amyloidosis and to FAI2, the french healthcare network for rare auto-immune and auto-inflammatory diseases.

More details @ Research Projects!

The team includes about 12 people- MD, Inserm and University/ENS researchers, Engineers, Post-doctoral fellows, PhD and Master students. We are always looking for highly motivated students to join the team and our research efforts-so please apply!

More details @ Team Members

Full updated list availabe @: Google Scholar

2022:

• Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism

Magnotti F, Chirita D, Dalmon S, Martin A, Bronnec P, Sousa J, Helynck O, Lee W, Kastner DL, Chae JJ, McDermott M, Belot A, Popoff M, Sève P, Georgin-Lavialle S, Munier-Lehmann H, Tran TA, De Langhe E, Wouters C, Jamilloux Y^@, Henry T^@(^@co-senior author)

Cell reports, 2022 Oct 11

2021:

• ALPK1 gene mutations drive autoinflammation with ectodermal dysplasia and progressive vision loss

Jamilloux Y, Mathis T, Grunewald O, Dollfuss H, Henry T, Sève P, Meunier I

Journal of Clinical Immunology, 2021 June 22

2020:

• A fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor

Magnotti F, Malsot T, Georgin-Lavialle S, Abbas F, Martin A, Belot A, Fauter M, Rabilloud M, Gerfaud-Valentin M, Sève P, Duquesne A, Hot A, Durupt S, Savey L, Giurgea I, Grateau G, Henry T^@, and Jamilloux Y^@ (^@co-senior author)

Annals of the Rheumatic Diseases, 2020 Oct 9

2019:

• Pyrin dephosphorylation is sufficient to trigger inflammasome activation in Familial Mediterranean Fever patients.

Magnotti F, Lefeuvre L, Benezech S, Malsot T, Waeckel L, Martin A, Kerever S, Chirita D, Desjonqueres M, Duquesne A, Gerfaud-Valentin M, Laurent A, Sève P, Popoff MR, Walzer T, Belot A, Jamilloux Y^@, Henry T^@ (^@co-senior author)

EMBO Mol Med. 2019 Oct 7

• A genome-wide screen identifies IRF2 as a key regulator of caspase-4 in human cells.

Benaoudia S, Martin A, Puig Gamez M, Gay G, Lagrange B, Cornut M, Krasnykov K, Claude JB, Bourgeois CF, Hughes S, Gillet B, Allatif O, Corbin A, Ricci R, Henry T.

EMBO Rep. 2019 Jul 29

2018:

• Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

Tromp AT, Van Gent M, Abrial P, Martin A, Jansen JP, De Haas CJC, Van Kessel KPM, Bardoel BW, Kruse E, Bourdonnay E, Boettcher M, McManus MT, Day CJ, Jennings MP, Lina G, Vandenesch F, Van Strijp JAG, Jan Lebbink R, Haas PA, Henry T^@, Spaan AN^@(^@co-senior author)

Nature Microbiol. 2018 May 7

• Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella highlighting functional differences with murine caspase-11

Lagrange B, Benaoudia S, Wallet P, Magnotti F, Provost A, Michal F, Martin A, Di Lorenzo F, Py FB, Molinaro A, Henry T

Nature Communications, 2018 Jan; 9 (1), 242

• Familial Mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome

Jamilloux Y*, Lefeuvre L*, Magnotti F*, Martin A, Benezech S, Allatif O, Penel-Page M, Hentgen V, Sève P,  Gerfaud-Valentin M, Duquesne A, Desjonquères M, Laurent A, Rémy-Piccolo V, Cimaz R, Cantarini L, Bourdonnay E, Walzer T, Py BF, Belot A, Henry T.

Rheumatology, 2018 Jan 1;57(1):100-111.

2017:

• 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, Golovlev 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 Pathogens, 2017 Oct2;13(10).

2016:

• Francisella tularensis IglG belongs to a novel family of PAAR-like T6SS proteins and harbors a unique N-terminal extension required for virulence

Rigard M, Bröms JE, Mosnier A, Hologne M, Martin A, Lindgren L, Punginelli C, Lays C, Walker O, Charbit A, Telouk P, Conlan W, Terradot L^@, Sjöstedt A^@, Henry T^@(^@co-senior author)

PLOS Pathogens, 2016, Aug 24

2015:

• Staphylococcus aureus targets the Duffy antigen receptor for chemokines (DARC) to lyse erythrocytes

Spaan AN*, Reyes-Robles T*, Badiou C, Cochet S, Boguslawski KM, Yoong P, Day CJ, de   Haas CJC, van Kessel KPM, Vandenesch F, Jennings MP, Le Van Kim C, Colin Y, van Strijp JAG, Henry T^@, and Torres VJ^@*Co-first, ^@Co-corresponding/Co-senior author

Cell Host and Microbes, 2015 Aug 26

• GBPs promote AIM2 inflammasome activation during Francisella infection by inducing cytosolic bacteriolysis and DNA release.

Meunier E*, Wallet P*, Dreier RF, Costanzo S, Anton L, Rühl S, Dick MS, Dussurgey S, Kistner A, Rigard M, Degrandi D, Pfeffer K, Yamamoto M, Henry T^@ and Broz P^@.#Co-first, ^@Co-corresponding author

Nature Immunology, 2015 Mar 16

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