1. Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization.
- Author
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Wu Y, Zeng Z, Guo Y, Song L, Weatherhead JE, Huang X, Zeng Y, Bimler L, Chang CY, Knight JM, Valladolid C, Sun H, Cruz MA, Hube B, Naglik JR, Luong AU, Kheradmand F, and Corry DB
- Subjects
- Blood Platelets metabolism, Hypersensitivity metabolism, Lymphocyte Activation immunology, T-Lymphocyte Subsets metabolism, Th17 Cells immunology, Th17 Cells metabolism, Th2 Cells immunology, Th2 Cells metabolism, Blood Platelets immunology, Candida albicans physiology, Candidiasis complications, Candidiasis immunology, Disease Susceptibility, Host-Pathogen Interactions immunology, Hypersensitivity complications, Hypersensitivity immunology, T-Lymphocyte Subsets immunology
- Abstract
Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and Th17 cell responses that correlated with reduced lung fungal burdens. Platelets simultaneously precluded lethal pulmonary hemorrhage resulting from fungal lung invasion. Thus, in addition to hemostasis, platelets promoted protection against C. albicans airway mycosis through an antifungal pathway involving candidalysin, GP1bα, and Dkk-1 that promotes Th2 and Th17 responses., Competing Interests: Declaration of interests D.B.C is a scientific consultant to Atrapos Therapeutics, LLC and Pulmocide, LLC., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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