title: A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection.
abstract: Candida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo. To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans.
authors.affiliation: Department of Pediatrics, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, Wisconsin, USA Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Huppler
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Whibley
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Woolford
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Childs
authors.affiliation: Department of Pediatrics, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Biswas
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: McGeachy
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
authors.affiliation: Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Sarah.Gaffen@pitt.edu.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D014774:Virulence / Q000276:immunology
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17