title: C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins.
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 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.
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: Michelle R
authors: MR
authors: Simpson-Abelson
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: Erin E
authors: EE
authors: Childs
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: M Carolina
authors: MC
authors: Ferreira
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: Shrinivas
authors: S
authors: Bishu
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: Heather R
authors: HR
authors: Conti
authors: Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, United States of America.
authors: Sarah L
authors: SL
authors: Gaffen
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002180:Candidiasis, Oral / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D020381:Interleukin-17; D023083:beta-Defensins