Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections

Area of Science:

• Immunology
• Neuroscience
• Gastroenterology

Background:

• The enteric nervous system (ENS) regulates crucial intestinal functions like motility.
• Infections can cause ENS damage, leading to neuropathies and motility disorders.
• Understanding protective mechanisms is vital for preserving gut health during infection.

Purpose of the Study:

• To investigate how the gut prevents neuronal loss and maintains motility after pathogen exposure.
• To identify the cellular and molecular pathways involved in infection-induced neuroprotection.

Main Methods:

• Studied mouse models of enteric bacterial and helminth infections.
• Analyzed the phenotype and function of muscularis macrophages (MMs).
• Investigated the roles of sympathetic neurons, adrenergic receptors, T cells, and cytokines (IL-4, IL-13) in neuroprotection.

Main Results:

• Following infection, muscularis macrophages (MMs) adopt a tissue-protective phenotype.
• Bacterial infections induced neuroprotection via sympathetic neuron activation and β2-adrenergic receptor (β2AR) signaling on MMs.
• Helminth infections triggered T cell and eosinophil-mediated protection through IL-4/IL-13, inducing arginase-expressing MMs.

Conclusions:

• Distinct enteric pathogens induce specific tolerance mechanisms to preserve ENS integrity.
• These mechanisms prevent neuronal loss and maintain gut motility during subsequent infections.
• The findings reveal novel pathways for maintaining gut health and function.