Candida Albicans Elicits Protective Allergic Responses Via Platelet Mediated T helper 2 and T helper 17 Cell Polarization

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

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)
92 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)2595-2610.e7
JournalImmunity
Volume54
Issue number11
Early online date9 Sept 2021
DOIs
Publication statusPublished - 9 Nov 2021

Fingerprint

Dive into the research topics of 'Candida Albicans Elicits Protective Allergic Responses Via Platelet Mediated T helper 2 and T helper 17 Cell Polarization'. Together they form a unique fingerprint.

Cite this