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Inter-tissue communication during nematode infections: role of dermal γδ17 T cells

Project description

Inter-tissue coordination of immune responses during helminth infections

Effective pathogen elimination has to include prevention from excessive collateral damage and requires the coordination of different types of immune responses within particular tissues. Reaching such equilibrium requires very complex coordination in cases of pathogens that migrate across different organs and tissues. The mechanism of coordination of immune responses between tissues is largely unexplored. Helminth infections provide unique models to investigate this process in cases when invasive larvae migrate across different organs to complete their life cycles. Funded by the Marie Skłodowska-Curie Actions programme, the INTERCONNECTION project will use nematode parasites, Nippostrongylus brasiliensis and Litomosoides sigmodontis, to investigate the coordination of the immune responses between different non-lymphoid tissues.

Objective

Complex multicellular organisms evolved to ensure that each tissue or organ responds appropriately to infectious challenge. Achieving pathogen elimination whilst preventing excessive collateral damage often requires the coordination of opposing types of immune responses (such as type-2 and type-17) within particular tissues. Reaching this equilibrium is even more complex when we consider pathogens that migrate across different organs. The mechanisms orchestrating immune responses between tissues, however, remain largely unexplored. Helminth infections provide great models to investigate this process as infective larvae migrate across different organs to complete their life cycles. In this proposal we will employ two distantly related nematode parasites, Nippostrongylus brasiliensis and Litomosoides sigmodontis, to identify and dissect the common mechanisms responsible for coordinating immune responses between different non-lymphoid tissues. Although exhibiting very distinct infection dynamics, both parasites induce host-protective type-2 immune responses, which are the result of an intricate cross-talk with type-17 immunity and poorly understood events early during infection. In addition, both nematodes have the skin as their entry site. Thus, we will employ state-of-the-art high-dimension techniques to generate an extensive phenotypical and topological characterization of the immune responses against nematode larvae in the skin. Moreover, a novel approach for local genetic manipulation of IL-17-producing dermal γδ T cells (the main orchestrators of skin type-17 immunity) will allow us to transpose the mechanisms of type-2/type-17 cross-talk to an inter-tissue dimension. Hence, by determining how skin immunity impacts the generation of systemic immune responses INTERCONNECTION will provide a new holistic view of nematode infections and open avenues of research that pave the way for immunization strategies of the future.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

THE UNIVERSITY OF MANCHESTER
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.

€ 212 933,76
Address
OXFORD ROAD
M13 9PL Manchester
United Kingdom

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Region
North West (England) Greater Manchester Manchester
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.

€ 212 933,76
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