Project description
Communication between the enteric nervous system and the immune system
Motor, sensory, absorptive and secretory functions of the gastrointestinal (GI) system are controlled by the GI’s nervous system, the enteric nervous system (ENS), which is the largest and most complex part of the peripheral nervous system. Infections can damage the ENS. However, the ENS is capable of immunomodulation, communicating with the immune system to ensure an adequate response to infection without overactivation, which can cause damage and enteric diseases. Little is known about the mechanisms of this communication. With the support of the Marie Skłodowska-Curie Actions programme, the GUT INSTINCT project aims to use human intestinal organoids to investigate this crosstalk during enteric infections of Trichuris trichiura and Trypanosoma cruzi.
Objective
The gastrointestinal (GI) tract has its own nervous system, known as the enteric nervous system (ENS), which contains a network of enteric neurons and glial cells and controls GI physiology and functions. Studies have shown inflammatory responses as a result of enteric infections can cause damage or injury to the ENS and an imbalance in the ENS can cause GI disorders. The fine modulation of the inflammatory responses induced by components of the innate immune system (e.g. macrophages) along with other key players of the immune system is essential to generate an adequate response to fight infections, while preventing overactivation which can cause irreparable GI pathology leading to enteric diseases. The ENS is capable of performing this immunomodulatory role and share a common language with the immune system to provide adequate protection from infections and maintain GI physiology. However, little is known about how the crosstalk between the two systems keep enteric infections at bay. In this study, I propose to investigate how the neuro-immune crosstalk regulate GI physiology during enteric infections of T. trichiura and T. cruzi from a human host perspective. To do this, I will use human intestinal organoids (HIOs). The use of HIOs in the field of infection biology holds great promise and offers tremendous potential to establish one unified system containing immune cells and the ENS. In this project, I will create an integrated HIO system containing the ENS and components of the innate immune system to investigate the neuro-immune crosstalk of enteric parasites using 3D cell culture, live imaging, immunofluorescence and advanced transcriptomic and protein profiling. This will in turn open up new avenues to study the infection biology of other pathogens, establish targeted therapies and develop personalised medicine.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiology
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
75654 Paris
France