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Metabolic control of immune cell function during fungal infection

Objective

The high mortality rates and healthcare costs associated with severe fungal infections highlight the urgent need to unveil their pathogenetic mechanisms and develop more effective diagnosis and treatment measures. Innate immunity has a key role in host response to fungal infection, by mediating fungal recognition and elimination, and modulating adaptive immune responses. The long pentraxin PTX3 is a soluble pattern recognition receptor that is involved in the recognition and opsonisation of Aspergillus fumigatus. Metabolism is a central regulator of immune cell function. Phagocytosis of A. fumigatus conidia elicits enhanced glycolysis in macrophages and is essential for optimal antifungal effector functions. Preliminary data from the host lab indicate that PTX3 deficiency, by compromising the metabolic reprogramming of macrophages, impairs phagocytosis, but also their conidiacidal capacity upon infection. Nevertheless, little is known about the mechanistic bases linking the functional activity of PTX3 and immune cell metabolism in the pathogenesis of fungal infection. In METAFUN, we propose to (i) define the molecular and cellular mechanisms whereby PTX3 regulates immune cell metabolism, (ii) dissect the spatiotemporal contribution of PTX3 to intracellular mechanisms of fungal clearance, and (iii) evaluate the contribution of PTX3 to fungicidal mechanisms in a human disease-relevant context using lung-on-a-chip systems. This original and interdisciplinary project will reveal previously unanticipated functions of PTX3 in antifungal immunity and will lay the foundations for the identification of new diagnostic and therapeutic targets for fungal disease.

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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-WIDERA-2022-TALENTS-04

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Coordinator

UNIVERSIDADE DO MINHO
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.

€ 156 778,56
Address
LARGO DO PACO
4704 553 Braga
Portugal

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Region
Continente Norte Cávado
Activity type
Higher or Secondary Education Establishments
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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.

No data

Partners (1)

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