Simpson-Abelson, MR and Childs, EE and Ferreira, MC and Bishu, S and Conti, HR and Gaffen, SL
(2015)
C/EBPβ promotes immunity to oral candidiasis through regulation of β-defensins.
PLoS ONE, 10 (8).
Abstract
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 cortisoneinduced 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. Copyright:
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Naglik, Julian R. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
28 August 2015 |
Date Type: |
Publication |
Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
Journal or Publication Title: |
PLoS ONE |
Volume: |
10 |
Number: |
8 |
DOI or Unique Handle: |
10.1371/journal.pone.0136538 |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Medicine > Immunology |
Refereed: |
Yes |
Date Deposited: |
23 Aug 2016 14:29 |
Last Modified: |
22 Jun 2021 15:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/28393 |
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