NHR-14 loss of function couples intestinal iron uptake with innate immunity in C. elegans through PQM-1 signaling

Abstract

Iron is essential for survival of most organisms. All organisms have thus developed mechanisms to sense, acquire and sequester iron. In C. elegans, iron uptake and sequestration are regulated by HIF-1. We previously showed that hif-1 mutants are developmentally delayed when grown under iron limitation. Here we identify nhr-14, encoding a nuclear receptor, in a screen conducted for mutations that rescue the developmental delay of hif-1 mutants under iron limitation. nhr-14 loss upregulates the intestinal metal transporter SMF-3 to increase iron uptake in hif-1 mutants. nhr-14 mutants display increased expression of innate immune genes and DAF-16/FoxO-Class II genes, and enhanced resistance to Pseudomonas aeruginosa. These responses are dependent on the transcription factor PQM-1, which localizes to intestinal cell nuclei in nhr-14 mutants. Our data reveal how C. elegans utilizes nuclear receptors to regulate innate immunity and iron availability, and show iron sequestration as a component of the innate immune response.

Data availability

RNA-seq data has been deposited in GEO under accession code GSE89783.In addition, raw RNA-seq data is reported in the source data files

The following data sets were generated

Article and author information

Author details

  1. Malini Rajan

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Cole P Anderson

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Paul M Rindler

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Steven Joshua Romney

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria C Ferreira dos Santos

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jason Gertz

    Department of Oncological Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Elizabeth A Leibold

    Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, United States
    For correspondence
    betty.leibold@genetics.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1000-9503

Funding

NIH Office of the Director (R01DK068602)

  • Elizabeth A Leibold

NIH Office of the Director (T32DK007115)

  • Cole P Anderson

NIH Office of the Director (T32DK007115)

  • Paul M Rindler

NIH Office of the Director (R00HG006922)

  • Jason Gertz

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

Reviewing Editor

  1. Bruno Lemaître, École Polytechnique Fédérale de Lausanne, Switzerland

Version history

  1. Received: April 8, 2019
  2. Accepted: September 17, 2019
  3. Accepted Manuscript published: September 18, 2019 (version 1)
  4. Version of Record published: October 4, 2019 (version 2)
  5. Version of Record updated: October 15, 2019 (version 3)

Copyright

© 2019, Rajan 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. Malini Rajan
  2. Cole P Anderson
  3. Paul M Rindler
  4. Steven Joshua Romney
  5. Maria C Ferreira dos Santos
  6. Jason Gertz
  7. Elizabeth A Leibold
(2019)
NHR-14 loss of function couples intestinal iron uptake with innate immunity in C. elegans through PQM-1 signaling
eLife 8:e44674.
https://doi.org/10.7554/eLife.44674

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https://doi.org/10.7554/eLife.44674

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