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

Elife. 2019 Sep 18:8:e44674. doi: 10.7554/eLife.44674.


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.

Keywords: C. elegans; NHR-14; PQM-1; SMF-3; cell biology; genetics; genomics; innate immunity; iron uptake; pathogen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Disease Resistance
  • Immunity, Innate*
  • Iron / metabolism*
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa / immunology*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction*
  • Trace Elements / metabolism
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • PQM-1 protein, C elegans
  • Receptors, Cytoplasmic and Nuclear
  • Trace Elements
  • Trans-Activators
  • Transcription Factors
  • nhr-14 protein, C elegans
  • Iron

Associated data

  • GEO/GSE89783