title: β-Defensin 1 plays a role in acute mucosal defense against Candida albicans.
abstract: 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.
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tomalka
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Department of Research, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106; and.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Azodi
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Hema P
authors.initials: HP
authors.lastname: Narra
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Krupen
authors.initials: K
authors.lastname: Patel
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Samantha
authors.initials: S
authors.lastname: O'Neill
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Cisley
authors.initials: C
authors.lastname: Cardwell
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hall
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Department of Research, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106; and amy.hise@case.edu.
authors.forename: Amy G
authors.identifier: http://orcid.org/0000-0001-5075-5792
authors.initials: AG
authors.lastname: Hise
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002180:Candidiasis, Oral / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D023083:beta-Defensins / Q000276:immunology*
chemical_list: C120555:Defb1 protein, mouse; D023083:beta-Defensins