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C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins
Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downst...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552893/ https://www.ncbi.nlm.nih.gov/pubmed/26317211 http://dx.doi.org/10.1371/journal.pone.0136538 |
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author | Simpson-Abelson, Michelle R. Childs, Erin E. Ferreira, M. Carolina Bishu, Shrinivas Conti, Heather R. Gaffen, Sarah L. |
author_facet | Simpson-Abelson, Michelle R. Childs, Erin E. Ferreira, M. Carolina Bishu, Shrinivas Conti, Heather R. Gaffen, Sarah L. |
author_sort | Simpson-Abelson, Michelle R. |
collection | PubMed |
description | Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream events that control immunity to this fungus are poorly understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBPβ is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBPβ in vivo is poorly understood, in part because C/EBPβ-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBPβ in the context of an IL-17-dependent immune response, using C. albicans infection as a model system. Confirming prior findings, we found that C/EBPβ is required for immunity to systemic candidiasis. In contrast, C/EBPβ(-/-) mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBPβ(-/-) mice experienced more severe OPC than WT mice in the context of cortisone-induced immunosuppression. Expression of the antimicrobial peptide β-defensin (BD)-3 correlated strongly with susceptibility in C/EBPβ(-/-) mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBPβ contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to β-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response. |
format | Online Article Text |
id | pubmed-4552893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45528932015-09-10 C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins Simpson-Abelson, Michelle R. Childs, Erin E. Ferreira, M. Carolina Bishu, Shrinivas Conti, Heather R. Gaffen, Sarah L. PLoS One Research Article Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream events that control immunity to this fungus are poorly understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBPβ is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBPβ in vivo is poorly understood, in part because C/EBPβ-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBPβ in the context of an IL-17-dependent immune response, using C. albicans infection as a model system. Confirming prior findings, we found that C/EBPβ is required for immunity to systemic candidiasis. In contrast, C/EBPβ(-/-) mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBPβ(-/-) mice experienced more severe OPC than WT mice in the context of cortisone-induced immunosuppression. Expression of the antimicrobial peptide β-defensin (BD)-3 correlated strongly with susceptibility in C/EBPβ(-/-) mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBPβ contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to β-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response. Public Library of Science 2015-08-28 /pmc/articles/PMC4552893/ /pubmed/26317211 http://dx.doi.org/10.1371/journal.pone.0136538 Text en © 2015 Simpson-Abelson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Simpson-Abelson, Michelle R. Childs, Erin E. Ferreira, M. Carolina Bishu, Shrinivas Conti, Heather R. Gaffen, Sarah L. C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title | C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title_full | C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title_fullStr | C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title_full_unstemmed | C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title_short | C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins |
title_sort | c/ebpβ promotes immunity to oral candidiasis through regulation of β-defensins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552893/ https://www.ncbi.nlm.nih.gov/pubmed/26317211 http://dx.doi.org/10.1371/journal.pone.0136538 |
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