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

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.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 995 000,00
Address
CALLE MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 995 000,00

Beneficiaries (1)

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