Investigating neuro-immune crosstalk during enteric parasitic infections using human intestinal organoids

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.