Parasites trigger epithelial cell crosstalk to drive gut-brain signalling

Area of Science:

• Neuroscience
• Immunology
• Gastroenterology

Background:

• Parasitic infections impact immune and sensory systems, but their collaborative mechanisms for protective behaviors are unclear.
• Gut sensory cells, like tuft cells and enterochromaffin (EC) cells, detect pathogens and irritants, influencing immune responses and pain signaling.
• Neuro-immune interactions and gut-brain communication are crucial for host defense.

Purpose of the Study:

• To investigate the paracrine signaling between gut sensory cells (tuft and EC cells) as a mechanism for neuro-immune interaction.
• To elucidate how acetylcholine (ACh) release from tuft cells influences EC cells and subsequent gut-brain communication.
• To understand the role of this signaling pathway in mediating protective behaviors during parasitic infections.

Main Methods:

• Investigated acetylcholine (ACh) release mechanisms from tuft cells.
• Examined the activation of muscarinic receptors on enterochromaffin (EC) cells by ACh.
• Assessed serotonin release from EC cells and its effect on vagal afferent neurons and food intake.

Main Results:

• Tuft cells exhibit two distinct ACh release modes: acute in response to parasite metabolites and constitutive 'leak-like' release during type 2 inflammation.
• Both ACh release modes activate muscarinic receptors on EC cells.
• Sustained ACh release leads to sufficient serotonin levels to stimulate vagal afferent neurons, suppressing food intake.

Conclusions:

• Paracrine signaling between tuft and EC cells is a key neuro-immune interaction mechanism.
• A two-phase signaling process involving ACh and serotonin regulates gut-brain communication during parasitic infections.
• This pathway explains the progression from asymptomatic to symptomatic parasitic disease and evokes protective behaviors like appetite suppression.