TRPM channels mediate learned pathogen avoidance following intestinal distention

  1. Adam Filipowicz
  2. Jonathan Lalsiamthara
  3. Alejandro Aballay  Is a corresponding author
  1. Oregon Health and Science University, United States

Abstract

Upon exposure to harmful microorganisms, hosts engage in protective molecular and behavioral immune responses, both of which are ultimately regulated by the nervous system. Using the nematode Caenorhabditis elegans, we show that ingestion of E. faecalis leads to a fast pathogen avoidance behavior that results in aversive learning. We have identified multiple sensory mechanisms involved in the regulation of avoidance of E. faecalis. The G-protein coupled receptor NPR-1-dependent oxygen-sensing pathway opposes this avoidance behavior, while an ASE neuron-dependent pathway and an AWB and AWC neuron-dependent pathway are directly required for avoidance. Colonization of the anterior part of the intestine by E. faecalis leads to AWB and AWC mediated olfactory aversive learning. Finally, two transient receptor potential melastatin (TRPM) channels, GON-2 and GTL-2, mediate this newly described rapid pathogen avoidance. These results suggest a mechanism by which TRPM channels may sense the intestinal distension caused by bacterial colonization to elicit pathogen avoidance and aversive learning by detecting changes in host physiology.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Adam Filipowicz

    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jonathan Lalsiamthara

    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alejandro Aballay

    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States
    For correspondence
    aballay@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5975-3352

Funding

National Institutes of Health (GM070907)

  • Alejandro Aballay

National Institutes of Health (AI156900)

  • Alejandro Aballay

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Douglas Portman, University of Rochester, United States

Version history

  1. Received: December 18, 2020
  2. Accepted: May 24, 2021
  3. Accepted Manuscript published: May 25, 2021 (version 1)
  4. Version of Record published: June 4, 2021 (version 2)

Copyright

© 2021, Filipowicz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Adam Filipowicz
  2. Jonathan Lalsiamthara
  3. Alejandro Aballay
(2021)
TRPM channels mediate learned pathogen avoidance following intestinal distention
eLife 10:e65935.
https://doi.org/10.7554/eLife.65935

Share this article

https://doi.org/10.7554/eLife.65935

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