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Functional characterisation of mitochondrial metabolic adaptations to innate sensing in dendritic cell subsets

Total Cost €


EC-Contrib. €






Project "MITOMAD" data sheet

The following table provides information about the project.


Organization address
city: MADRID
postcode: 28029

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Total cost 1˙995˙000 €
 EC max contribution 1˙995˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-12-01   to  2022-11-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Immunometabolism is an emerging research field that promises to generate novel targets for manipulation of functional responses in immune cells. Pioneering studies are beginning to unveil how innate sensing leads to metabolic reprogramming of immune cells. We became interested in the possible metabolic consequences of innate sensing by myeloid cells because of our previous work showing how mouse and human dendritic cell (DC) subsets detect danger signals from microbes and damaged tissues. Our current data show that sensing of live bacteria triggers a profound reorganisation of the mitochondrial electron transport chain (ETC) in macrophages, with a switch in the relative contribution of ETC complexes I and II to mitochondrial respiration that impacts immune response. As we pursue novel strategies to manipulate DC function, and supported by our preliminary data in DCs, we hypothesise that innate sensing induces mitochondrial adaptations in DCs and that targeting mitochondrial metabolism will affect DC function. Our goals are: 1) to characterise how innate sensing of danger signals from microbes or from tissue damage modulate mitochondrial adaptations and metabolic reprogramming in mouse and human DC subsets; 2) to dissect the molecular mechanisms that connect innate sensing and mitochondrial adaptations in DCs, using biased and unbiased cutting-edge proteomics approaches; 3) to address the impact of manipulating mitochondrial biology on mouse and human DC metabolism and function; and 4) to assess the functional in vivo effects of targeting mitochondrial biology in DCs in homeostasis and disease. The characterisation of the molecular mechanisms that link innate sensing and mitochondrial metabolism with DC function will open new avenues for basic research in mitochondrial biology and for the emerging field of immunometabolism. Functional targeting of DC mitochondrial metabolism has great potential for the discovery of new strategies to modulate immunity and tolerance.


year authors and title journal last update
List of publications.
2018 Tamara Girbl, Tchern Lenn, Lorena Perez, Loïc Rolas, Anna Barkaway, Aude Thiriot, Carlos del Fresno, Eleanor Lynam, Elin Hub, Marcus Thelen, Gerard Graham, Ronen Alon, David Sancho, Ulrich H. von Andrian, Mathieu-Benoit Voisin, Antal Rot, Sussan Nourshargh
Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis
published pages: 1062-1076.e6, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2018.09.018
Immunity 49/6 2019-09-02
2018 Carlos del Fresno, Paula Saz-Leal, Michel Enamorado, Stefanie K. Wculek, Sarai Martínez-Cano, Noelia Blanco-Menéndez, Oliver Schulz, Mattia Gallizioli, Francesc Miró-Mur, Eva Cano, Anna Planas, David Sancho
DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment
published pages: 351-356, ISSN: 0036-8075, DOI: 10.1126/science.aan8423
Science 362/6412 2019-09-02
2018 Carlos del Fresno, Salvador Iborra, Paula Saz-Leal, María Martínez-López, David Sancho
Flexible Signaling of Myeloid C-Type Lectin Receptors in Immunity and Inflammation
published pages: 804, ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00804
Frontiers in Immunology 9 2019-09-02
2019 Stefanie K. Wculek, Joaquín Amores-Iniesta, Ruth Conde-Garrosa, Sofía C. Khouili, Ignacio Melero, David Sancho
Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen
published pages: 100, ISSN: 2051-1426, DOI: 10.1186/s40425-019-0565-5
Journal for ImmunoTherapy of Cancer 7/1 2019-09-02
2019 Carlos del Fresno, David Sancho
cDC1s: New Orchestrators of Tissue Innate Immunity
published pages: 559-561, ISSN: 1471-4906, DOI: 10.1016/
Trends in Immunology 40/7 2019-09-02
2018 Helena M. Izquierdo, Paola Brandi, Manuel-José Gómez, Ruth Conde-Garrosa, Elena Priego, Michel Enamorado, Sarai Martínez-Cano, Iria Sánchez, Laura Conejero, Daniel Jimenez-Carretero, Silvia Martín-Puig, Martin Guilliams, David Sancho
Von Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal Differentiation, Self-Renewal, and Function
published pages: 1738-1746, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.07.034
Cell Reports 24/7 2019-09-02
2018 María Martínez-López, Manuel Soto, Salvador Iborra, David Sancho
Leishmania Hijacks Myeloid Cells for Immune Escape
published pages: 883, ISSN: 1664-302X, DOI: 10.3389/fmicb.2018.00883
Frontiers in Microbiology 9 2019-09-02
2018 Michel Enamorado, Sofía C. Khouili, Salvador Iborra, David Sancho
Genealogy, Dendritic Cell Priming, and Differentiation of Tissue-Resident Memory CD8+ T Cells
published pages: 1751, ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.01751
Frontiers in Immunology 9 2019-09-02
2018 Dieke van Dinther, Henrike Veninga, Salvador Iborra, Ellen G.F. Borg, Leoni Hoogterp, Katarzyna Olesek, Marieke R. Beijer, Sjoerd T.T. Schetters, Hakan Kalay, Juan J. Garcia-Vallejo, Kees L. Franken, Lamin B. Cham, Karl S. Lang, Yvette van Kooyk, David Sancho, Paul R. Crocker, Joke M.M. den Haan
Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming
published pages: 1484-1495, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.01.021
Cell Reports 22/6 2019-09-04
2019 Stefanie K. Wculek, Sofía C. Khouili, Elena Priego, Ignacio Heras-Murillo, David Sancho
Metabolic Control of Dendritic Cell Functions: Digesting Information
published pages: 775, ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.00775
Frontiers in Immunology 10 2019-09-02
2018 Maria M. M. Kaisar, Manuel Ritter, Carlos del Fresno, Hulda S. Jónasdóttir, Alwin J. van der Ham, Leonard R. Pelgrom, Gabriele Schramm, Laura E. Layland, David Sancho, Clarissa Prazeres da Costa, Martin Giera, Maria Yazdanbakhsh, Bart Everts
Dectin-1/2–induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses
published pages: e2005504, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.2005504
PLOS Biology 16/4 2019-09-02
2019 José M. Adrover, Carlos del Fresno, Georgiana Crainiciuc, Maria Isabel Cuartero, María Casanova-Acebes, Linnea A. Weiss, Hector Huerga-Encabo, Carlos Silvestre-Roig, Jan Rossaint, Itziar Cossío, Ana V. Lechuga-Vieco, Jaime García-Prieto, Mónica Gómez-Parrizas, Juan A. Quintana, Ivan Ballesteros, Sandra Martin-Salamanca, Alejandra Aroca-Crevillen, Shu Zhen Chong, Maximilien Evrard, Karl Balab
A Neutrophil Timer Coordinates Immune Defense and Vascular Protection
published pages: 390-402.e10, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2019.01.002
Immunity 50/2 2019-09-02
2019 María Martínez-López, Salvador Iborra, Ruth Conde-Garrosa, Annalaura Mastrangelo, Camille Danne, Elizabeth R. Mann, Delyth M. Reid, Valérie Gaboriau-Routhiau, Maria Chaparro, María P. Lorenzo, Lara Minnerup, Paula Saz-Leal, Emma Slack, Benjamin Kemp, Javier P. Gisbert, Andrzej Dzionek, Matthew J. Robinson, Francisco J. Rupérez, Nadine Cerf-Bensussan, Gordon D. Brown, David Bernardo, Salomé
Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity
published pages: 446-461.e9, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2018.12.020
Immunity 50/2 2019-09-02
2018 Paula Saz-Leal, Carlos del Fresno, Paola Brandi, Sarai Martínez-Cano, Otto M. Dungan, John D. Chisholm, William G. Kerr, David Sancho
Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection
published pages: 1118-1126, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.09.092
Cell Reports 25/5 2019-09-02

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