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Identification of glucocorticoid receptor in Drosophila melanogaster
BACKGROUND: Vertebrate glucocorticoid receptor (GR) is an evolutionary-conserved cortisol-regulated nuclear receptor that controls key metabolic and developmental pathways. Upon binding to cortisol, GR acts as an immunosuppressive transcription factor. Drosophila melanogaster, a model organism to st...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296755/ https://www.ncbi.nlm.nih.gov/pubmed/32539689 http://dx.doi.org/10.1186/s12866-020-01848-x |
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author | Bartolo, Gloria Gonzalez, Leandra O. Alameh, Saleem Valencia, C. Alexander Martchenko Shilman, Mikhail |
author_facet | Bartolo, Gloria Gonzalez, Leandra O. Alameh, Saleem Valencia, C. Alexander Martchenko Shilman, Mikhail |
author_sort | Bartolo, Gloria |
collection | PubMed |
description | BACKGROUND: Vertebrate glucocorticoid receptor (GR) is an evolutionary-conserved cortisol-regulated nuclear receptor that controls key metabolic and developmental pathways. Upon binding to cortisol, GR acts as an immunosuppressive transcription factor. Drosophila melanogaster, a model organism to study innate immunity, can also be immunosuppressed by glucocorticoids. However, while the genome of fruit fly harbors 18 nuclear receptor genes, the functional homolog of vertebrate GR has not been identified. RESULTS: In this study, we demonstrated that while D. melanogaster is susceptible to Saccharomyces cerevisiae oral infection, the oral exposure to cortisol analogs, cortisone acetate or estrogen, increases fly sensitivity to yeast challenge. To understand the mechanism of this steroid-induced immunosuppression, we identified the closest genetic GR homolog as D. melanogaster Estrogen Related Receptor (ERR) gene. We discovered that Drosophila ERR is necessary for cortisone acetate- and estrogen-mediated increase in sensitivity to fungal infection: while ERR mutant flies are as sensitive to the fungal challenge as the wildtype flies, the yeast-sensitivity of ERR mutants is not increased by these steroids. Interestingly, the fungal cortisone analog, ergosterol, did not increase the susceptibility of Drosophila to yeast infection. The immunosuppressive effect of steroids on the sensitivity of flies to fungi is evolutionary conserved in insects, as we show that estrogen significantly increases the yeast-sensitivity of Culex quinquefasciatus mosquitoes, whose genome contains a close ortholog of the fly ERR gene. CONCLUSIONS: This study identifies a D. melanogaster gene that structurally resembles vertebrate GR and is functionally necessary for the steroid-mediated immunosuppression to fungal infections. |
format | Online Article Text |
id | pubmed-7296755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72967552020-06-16 Identification of glucocorticoid receptor in Drosophila melanogaster Bartolo, Gloria Gonzalez, Leandra O. Alameh, Saleem Valencia, C. Alexander Martchenko Shilman, Mikhail BMC Microbiol Research Article BACKGROUND: Vertebrate glucocorticoid receptor (GR) is an evolutionary-conserved cortisol-regulated nuclear receptor that controls key metabolic and developmental pathways. Upon binding to cortisol, GR acts as an immunosuppressive transcription factor. Drosophila melanogaster, a model organism to study innate immunity, can also be immunosuppressed by glucocorticoids. However, while the genome of fruit fly harbors 18 nuclear receptor genes, the functional homolog of vertebrate GR has not been identified. RESULTS: In this study, we demonstrated that while D. melanogaster is susceptible to Saccharomyces cerevisiae oral infection, the oral exposure to cortisol analogs, cortisone acetate or estrogen, increases fly sensitivity to yeast challenge. To understand the mechanism of this steroid-induced immunosuppression, we identified the closest genetic GR homolog as D. melanogaster Estrogen Related Receptor (ERR) gene. We discovered that Drosophila ERR is necessary for cortisone acetate- and estrogen-mediated increase in sensitivity to fungal infection: while ERR mutant flies are as sensitive to the fungal challenge as the wildtype flies, the yeast-sensitivity of ERR mutants is not increased by these steroids. Interestingly, the fungal cortisone analog, ergosterol, did not increase the susceptibility of Drosophila to yeast infection. The immunosuppressive effect of steroids on the sensitivity of flies to fungi is evolutionary conserved in insects, as we show that estrogen significantly increases the yeast-sensitivity of Culex quinquefasciatus mosquitoes, whose genome contains a close ortholog of the fly ERR gene. CONCLUSIONS: This study identifies a D. melanogaster gene that structurally resembles vertebrate GR and is functionally necessary for the steroid-mediated immunosuppression to fungal infections. BioMed Central 2020-06-15 /pmc/articles/PMC7296755/ /pubmed/32539689 http://dx.doi.org/10.1186/s12866-020-01848-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Bartolo, Gloria Gonzalez, Leandra O. Alameh, Saleem Valencia, C. Alexander Martchenko Shilman, Mikhail Identification of glucocorticoid receptor in Drosophila melanogaster |
title | Identification of glucocorticoid receptor in Drosophila melanogaster |
title_full | Identification of glucocorticoid receptor in Drosophila melanogaster |
title_fullStr | Identification of glucocorticoid receptor in Drosophila melanogaster |
title_full_unstemmed | Identification of glucocorticoid receptor in Drosophila melanogaster |
title_short | Identification of glucocorticoid receptor in Drosophila melanogaster |
title_sort | identification of glucocorticoid receptor in drosophila melanogaster |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296755/ https://www.ncbi.nlm.nih.gov/pubmed/32539689 http://dx.doi.org/10.1186/s12866-020-01848-x |
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