Immune Response and Danger Signals
Bénédicte Manoury
Team description
The aim of our work is to deepen our understanding of mononuclear phagocytes (dendritic cells, macrophages, and monocytes) in health and disease. We seek to harness this knowledge to manipulate these cells for therapeutic benefit, particularly in cancer and inflammatory disorders. To this end, we combine analyses of human cells freshly isolated from tissues, in vitro models, computational approaches, and in vivo studies in mice. Our work relies on state-of-the-art technologies, including high-dimensional spectral flow cytometry and imaging, proteomics, bulk and single-cell transcriptomics, and CRISPR-based gene editing.
Our main research projects focus on:
- Investigating how Pattern Recognition Receptors (PRR), particularly intracellular Toll-like receptors (TLR), trafficking and signalling, are regulated at the steady state and during inflammation in myeloid cells. PRR recognize microbial products and play an essential role in innate and adaptive immunity. In particular, we focus on nucleic acids-sensing PRR, which require proteolytic cleavage to be functional and recruit adaptor proteins. Our objective is to identify new interaction partners of these PRR.
- Elucidating the role of TLR9 in immune tolerance, anti-tumor immunity, and neuroinflammatory pathologies such as Alzheimer’s disease.
- Characterizing the properties of monocytes and monocyte-derived cells in tissues. Despite recent progress, our knowledge of the functional specialization of monocytes, and monocyte-derived macrophages and dendritic cells remains incomplete. In particular, the features of monocyte-derived macrophages in tissue repair remain poorly understood, as well as the role of monocytes in anti-cancer responses.
- Deciphering the role of Aryl Hydrocarbon Receptor in mononuclear phagocytes. Aryl Hydrocarbon Receptor is involved in lymphoid cells differentiation and function, but its role in mononuclear phagocytes is not fully understood. In addition, how dietary agonists impact immune cells outside of the intestine via activation of the Aryl Hydrocarbon Receptor is also unclear.
- Analyzing the cellular interactions between mononuclear phagocytes and T cell subsets (helper, cytotoxic, and regulatory) as well as natural killer (NK) cells. We aim to uncover their underlying molecular mechanisms, both at steady state and in pathological settings such as cancer, inflammatory and autoimmune diseases, and normal versus complicated pregnancy.
Key publications
de Juan A, Tabtim-On D, Coillard A, Becher B, Goudot C, Segura E.
The aryl hydrocarbon receptor shapes monocyte transcriptional responses to interleukin-4 by prolonging STAT6 binding to promoters.
Sci Signal.
2024;
Oct 15;17(858):eadn6324.
doi:
10.1126/scisignal.adn6324.
PMID: 39405377
.
de Lavergne M, Maisonneuve L, Podsypanina K, Manoury B.
The role of the antigen processing machinery in the regulation and trafficking of intracellular -Toll-like receptor molecules.
Curr Opin Immunol.
2023;
Oct;84:102375. Epub 2023 Aug 8.
doi:
10.1016/j.coi.2023.102375.
PMID: 37562076
.
Alaoui L, Villar J, Leclere R, Le Gallou S, Relouzat F, Michaud HA, Tarte K, Teissier N, Favier B, Roussel M, Segura E.
Functional specialization of short-lived and long-lived macrophage subsets in human tonsils.
J Exp Med.
2023;
Jul 3;220(7):e20230002. Epub 2023 Apr 10.
doi:
10.1084/jem.20230002.
PMID: 37036425
;
PMCID: PMC10098144.
Villar J, Cros A, De Juan A, Alaoui L, Bonte PE, Lau CM, Tiniakou I, Reizis B, Segura E.
ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment.
Nat Immunol.
2023;
Jan;24(1):84-95. Epub 2022 Dec 21.
doi:
10.1038/s41590-022-01374-0.
PMID: 36543959
;
PMCID: PMC9810530.
Tohme M, Maisonneuve L, Achour K, Dussiot M, Maschalidi S, Manoury B.
TLR7 trafficking and signaling in B cells is regulated by the MHCII-associated invariant chain.
J Cell Sci.
2021;
Oct 15;134(20).
doi:
10.1242/jcs.236711.
PMID: 32079661
.
Maatouk L, Compagnion AC, Sauvage MC, Bemelmans AP, Leclere-Turbant S, Cirotteau V, Tohme M, Beke A, Trichet M, Bazin V, Trawick BN, Ransohoff RM, Tronche F, Manoury B, Vyas S.
TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons.
Nat Commun.
2018 Jun 22;9(1):2450.
doi:
10.1038/s41467-018-05680-w.
PMID: 30068993
;
PMCID: PMC6070486.
Maschalidi S, Nunes-Hasler P, Nascimento CR, Sallent I, Lannoy V, Garfa-Traore M, Cagnard N, Sepulveda FE, Vargas P, Lennon-Duménil AM, van Endert P, Capiod T, Demaurex N, Darrasse-Jèze G, Manoury B.
UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells.
Nat Commun.
2017;
Nov 21;8(1):1640.
doi:
10.1038/s41467-017-01601-5.
PMID: 29158474
;
PMCID: PMC5696382.
Team leader