C/EBP[beta] Promotes Immunity to Oral Candidiasis through Regulation of [beta]-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...

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Bibliographic Details
Published in:PloS one 2015-08, Vol.10 (8)
Main Authors: Bishu, Shrinivas, Conti, Heather R, Childs, Erin E, Simpson-Abelson, Michelle R, Ferreira, M. Carolina, Gaffen, Sarah L
Format: Article
Language:English
Subjects:
Candidiasis
Cellular signal transduction
Development and progression
Disease susceptibility
Genetic aspects
Health aspects
Mouth diseases
Transcription factors
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Summary: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-[beta] (C/EBP[beta]) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBP[beta] is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBP[beta] in vivo is poorly understood, in part because C/EBP[beta]-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBP[beta] 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/EBP[beta] is required for immunity to systemic candidiasis. In contrast, C/EBP[beta].sup.-/- mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBP[beta].sup.-/- mice experienced more severe OPC than WT mice in the context of cortisone-induced immunosuppression. Expression of the antimicrobial peptide [beta]-defensin (BD)-3 correlated strongly with susceptibility in C/EBP[beta].sup.-/- mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBP[beta] contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to [beta]-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response.
ISSN:1932-6203
1932-6203