title: Polyclonal anti-Candida antibody improves phagocytosis and overall outcome in zebrafish model of disseminated candidiasis.
abstract: Fungal infections are a major cause of animal and plant morbidity and mortality worldwide. Effective biological therapeutics could complement current antifungal drugs, but understanding of their in vivo mechanisms has been hampered by technical barriers to intravital imaging of host-pathogen interactions. Here we characterize the fungal infection of zebrafish as a model to understand the mechanism-of-action for biological antifungal therapeutics through intravital imaging of these transparent animals. We find that non-specific human IgG enhances phagocytosis by zebrafish phagocytes in vivo. Polyclonal anti-Candida antibodies enhance containment of fungi in vivo and promote survival. Analysis suggests that early phagocytic containment is a strong prognostic indicator for overall survival. Although polyclonal anti-Candida antibodies protect against disease, this is not necessarily the case for individual monoclonal anti-Candida antibodies. Thus, the zebrafish appears to provide a useful model host for testing if a biological therapeutic promotes phagocytosis in vivo and enhances protection against candidemia.
authors.affiliation: Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469, United States.
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Bergeron
authors.affiliation: Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Barker
authors.affiliation: Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469, United States.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Brothers
authors.affiliation: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Rd, Tarrytown, NY 10591, United States.
authors.forename: Brinda C
authors.initials: BC
authors.lastname: Prasad
authors.affiliation: Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469, United States; Graduate School of Biomedical Sciences, University of Maine, Orono, ME 04469, United States. Electronic address: robert.wheeler1@maine.edu.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005393:Fish Diseases / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D015027:Zebrafish / Q000276:immunology*
chemical_list: D000908:Antibodies, Fungal; D007074:Immunoglobulin G
keywords: Antibody; Candida; Innate immunity; Phagocytosis; Zebrafish