β-Defensin 1 plays a role in acute mucosal defense against Candida albicans

• Published in: The Journal of immunology (1950) Vol. 194; no. 4; pp. 1788 - 1795
• Main Authors: Tomalka, Jeffrey, Azodi, Elaheh, Narra, Hema P, Patel, Krupen, O'Neill, Samantha, Cardwell, Cisley, Hall, Brian A, Wilson, James M, Hise, Amy G
• Format: Journal Article
• Language: English
• Published: United States 15-02-2015
• Subjects: Animals; beta-Defensins - immunology; Candida albicans; Candida albicans - immunology; Candidiasis, Oral - immunology; Immunity, Innate - immunology; Immunity, Mucosal - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Real-Time Polymerase Chain Reaction
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203239

Candida is an opportunistic fungal pathogen that colonizes the mucosal tract of humans. Pathogenic infection occurs in the presence of conditions causing perturbations to the commensal microbiota or host immunity. Early innate immune responses by the epithelium, including antimicrobial peptides (AMPs) and cytokines, are critical for protection against overgrowth. Reduced salivary AMP levels are associated with oral Candida infection, and certain AMPs, including human β-defensins 1-3, have direct fungicidal activity. In this study, we demonstrate that murine β-defensin 1 (mBD1) is important for control of early mucosal Candida infection and plays a critical role in the induction of innate inflammatory mediators. Mice deficient in mBD1, as compared with wild-type mice, exhibit elevated oral and systemic fungal burdens. Neutrophil infiltration to the sites of mucosal Candida invasion, an important step in limiting fungal infection, is significantly reduced in mBD1-deficient mice. These mice also exhibit defects in the expression of other AMPs, including mBD2 and mBD4, which may have direct anti-Candida activity. We also show that mBD1 deficiency impacts the production of important antifungal inflammatory mediators, including IL-1β, IL-6, KC, and IL-17. Collectively, these studies demonstrate a role for the mBD1 peptide in early control of Candida infection in a murine model of mucosal candidiasis, as well as in the modulation of host immunity through augmentation of leukocyte infiltration and inflammatory gene regulation.