Candida albicans Elicits Protective Allergic Responses via Platelet Mediated T Helper 2 and T Helper 17 Cell Polarization

Authors

Yifan Wu
Zhimin Zeng
Yubiao Guo
Lizhen Song
Jill E Weatherhead
Xinyan Huang
Yuying Zeng
Lynn Bimler
Cheng-Yen Chang
John M Knight
Christian Valladolid
Hua Sun
Miguel A Cruz
Bernhard Hube
Julian R Naglik
Amber U Luong
Farrah Kheradmand
David B Corry

Publication Date

11-9-2021

Journal

Immunity

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.

Keywords

Blood Platelets, Candida albicans, Candidiasis, Disease Susceptibility, Host-Pathogen Interactions, Hypersensitivity, Lymphocyte Activation, T-Lymphocyte Subsets, Th17 Cells, Th2 Cells

Comments

PMID: 34506733