Role of Hepcidin in Protection Against Systemic Dissemination During Oropharyngeal Candida albicans Infection

Abstract

Candida albicans (C. albicans) is a commensal fungus that can cause mucosal and systemic disease when host immunity or microbiota balance is disrupted. Hepcidin is a hepatic peptide hormone that degrades the iron exporter ferroportin, restricts extracellular iron availability, and forms a key component of nutritional immunity. This study investigated how hepcidin deficiency alters oral colonization and systemic dissemination of C. albicans in a murine model of oropharyngeal candidiasis (OPC). Inducible hepcidin knockout (iHamp-/-) and wild-type (WT) mice were immunosuppressed with cortisone acetate and sublingually inoculated with C. albicans SC5314. Fungal burden, weight loss, expression of inflammatory genes (NGAL, IL-6, IFN-γ), and leukocyte populations were quantified by CFU plating, qPCR, and multicolor flow cytometry, respectively. Across both genotypes, the oral cavity carried the highest overall fungal burden. WT mice exhibited greater fungal burden in the tongue and pronounced weight loss. In comparison, iHamp-/- mice exhibited higher fungal burden in the kidney, indicating exacerbated dissemination, increased inflammation (as indicated by increased IL6 expression in the tongue and kidney), and injury (as indicated by increased NGAL expression in the kidney). Lymphocyte recruitment to affected tissues was comparable. Together, these results indicate a yet-to-be-defined protective role of hepcidin deficiency in oropharyngeal candidiasis.