NHR-14 loss of function couples intestinal iron uptake with innate immunity in C. elegans through PQM-1 signaling
| Autor: | Jason Gertz, Paul M Rindler, Elizabeth A. Leibold, Maria C Ferreira dos Santos, Malini Rajan, Cole P. Anderson, Steven J. Romney |
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| Rok vydání: | 2019 |
| Předmět: |
Mutant
Receptors Cytoplasmic and Nuclear SMF-3 0302 clinical medicine Sense (molecular biology) Biology (General) PQM-1 innate immunity Disease Resistance 0303 health sciences General Neuroscience General Medicine Cell biology DNA-Binding Proteins Pseudomonas aeruginosa C. elegans Medicine Research Article Signal Transduction animal structures QH301-705.5 Science Iron Biology NHR-14 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Animals Pseudomonas Infections Caenorhabditis elegans Caenorhabditis elegans Proteins Gene Transcription factor Loss function 030304 developmental biology Innate immune system General Immunology and Microbiology iron uptake Genetics and Genomics Biological Transport Transporter Cell Biology Immunity Innate Trace Elements Nuclear receptor Trans-Activators 030217 neurology & neurosurgery pathogen Transcription Factors |
| Zdroj: | eLife eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.44674 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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