NHR-14 loss of function couples intestinal iron uptake with innate immunity in C. elegans through PQM-1 signaling
- University of Utah, United States
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
Article and author information
Author details
Elizabeth A Leibold
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
- Bruno Lemaître, École Polytechnique Fédérale de Lausanne, Switzerland
Version history
- Received: April 8, 2019
- Accepted: September 17, 2019
- Accepted Manuscript published: September 18, 2019 (version 1)
- Version of Record published: October 4, 2019 (version 2)
- 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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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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