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TRPM channels mediate learned pathogen avoidance following intestinal distention.

Adam Filipowicz1, Jonathan Lalsiamthara1, Alejandro Aballay1

  • 1Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, United States.

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|May 25, 2021
PubMed
Summary

The nervous system regulates immune responses. In C. elegans, ingesting Enterococcus faecalis triggers pathogen avoidance and aversive learning, mediated by TRPM channels sensing gut distension.

Keywords:
C. elegansTRPM channelsaversive learninghost physiologyinfectious diseasemicrobiologyneuroscienceolfactory aversive learningpathogen avoidance

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Area of Science:

  • Neuroscience
  • Immunology
  • Microbiology
  • Genetics

Background:

  • Host immune responses involve molecular and behavioral strategies regulated by the nervous system.
  • Pathogen avoidance is a critical host defense mechanism.
  • The nematode Caenorhabditis elegans serves as a model organism for studying conserved biological processes.

Purpose of the Study:

  • To investigate the neural mechanisms underlying pathogen avoidance behavior in response to Enterococcus faecalis in C. elegans.
  • To identify sensory pathways and molecular players involved in rapid pathogen avoidance and aversive learning.
  • To elucidate the role of transient receptor potential melastatin (TRPM) channels in sensing bacterial colonization and initiating avoidance.

Main Methods:

  • Behavioral assays to measure pathogen avoidance and aversive learning in C. elegans exposed to E. faecalis.
  • Genetic analysis using mutant strains to identify genes and neurons involved in avoidance.
  • Optogenetic and chemogenetic tools to manipulate neural activity.
  • Microscopy to visualize bacterial colonization and host-pathogen interactions.

Main Results:

  • Ingestion of E. faecalis induces rapid pathogen avoidance behavior and olfactory aversive learning in C. elegans.
  • Avoidance is regulated by multiple sensory pathways, including ASE, AWB, and AWC neurons.
  • The NPR-1 oxygen-sensing pathway opposes E. faecalis avoidance.
  • Colonization of the anterior intestine by E. faecalis triggers AWB and AWC neuron-dependent aversive learning.
  • Two TRPM channels, GON-2 and GTL-2, are essential for mediating rapid pathogen avoidance.

Conclusions:

  • TRPM channels (GON-2, GTL-2) play a crucial role in sensing intestinal distension caused by bacterial colonization.
  • This sensing mechanism elicits pathogen avoidance and aversive learning by detecting host physiological changes.
  • The nervous system integrates signals from gut colonization to orchestrate protective behavioral responses against pathogens.