Summary
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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| Web resources: | https://cordis.europa.eu/project/id/101025781 |
| Start date: | 01-01-2022 |
| End date: | 31-12-2023 |
| Total budget - Public funding: | 212 933,76 Euro - 212 933,00 Euro |
Cordis data
Original description
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.Status
SIGNEDCall topic
MSCA-IF-2020Update Date
28-04-2024
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