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Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling
Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage. Methods. Using reconstituted oral epithelium, we assessed epithelial gen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017362/ https://www.ncbi.nlm.nih.gov/pubmed/24357630 http://dx.doi.org/10.1093/infdis/jit824 |
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author | Moyes, David L. Shen, Chengguo Murciano, Celia Runglall, Manohursingh Richardson, Jonathan P. Arno, Matthew Aldecoa-Otalora, Estibaliz Naglik, Julian R. |
author_facet | Moyes, David L. Shen, Chengguo Murciano, Celia Runglall, Manohursingh Richardson, Jonathan P. Arno, Matthew Aldecoa-Otalora, Estibaliz Naglik, Julian R. |
author_sort | Moyes, David L. |
collection | PubMed |
description | Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage. Methods. Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans–induced damage protection was determined using chemical inhibitors. Results. Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation. Conclusions. PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling. |
format | Online Article Text |
id | pubmed-4017362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40173622014-05-12 Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling Moyes, David L. Shen, Chengguo Murciano, Celia Runglall, Manohursingh Richardson, Jonathan P. Arno, Matthew Aldecoa-Otalora, Estibaliz Naglik, Julian R. J Infect Dis Major Articles and Brief Reports Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage. Methods. Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans–induced damage protection was determined using chemical inhibitors. Results. Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation. Conclusions. PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling. Oxford University Press 2014-06-01 2013-12-19 /pmc/articles/PMC4017362/ /pubmed/24357630 http://dx.doi.org/10.1093/infdis/jit824 Text en © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Major Articles and Brief Reports Moyes, David L. Shen, Chengguo Murciano, Celia Runglall, Manohursingh Richardson, Jonathan P. Arno, Matthew Aldecoa-Otalora, Estibaliz Naglik, Julian R. Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title | Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title_full | Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title_fullStr | Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title_full_unstemmed | Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title_short | Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling |
title_sort | protection against epithelial damage during candida albicans infection is mediated by pi3k/akt and mammalian target of rapamycin signaling |
topic | Major Articles and Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017362/ https://www.ncbi.nlm.nih.gov/pubmed/24357630 http://dx.doi.org/10.1093/infdis/jit824 |
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