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 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(-/-) mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBP beta(-/-) 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(-/-) 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.