Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization.

Sep 13, 2021

Contributor: 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

Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization.

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.
Copyright © 2021 Elsevier Inc. All rights reserved.

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About The Expert

Yifan Wu

Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Zhimin Zeng

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Yubiao Guo

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Lizhen Song

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Jill E Weatherhead

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Xinyan Huang

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Yuying Zeng

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Lynn Bimler

Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Cheng-Yen Chang

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Translational Biology and Molecular Medicine Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

John M Knight

Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Christian Valladolid

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular Physiology & Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas, 77030, USA.

Hua Sun

Department of Otolaryngology, McGovern Medical School of the University of Texas Health Science Center at Houston, Houston, Texas, USA.

Miguel A Cruz

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas, 77030, USA.

Bernhard Hube

Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knoell Institute Jena (HKI), Jena 07745, Germany; Institute of Microbiology, Friedrich Schiller University, Jena 07737, Germany.

Julian R Naglik

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK.

Amber U Luong

Department of Otolaryngology, McGovern Medical School of the University of Texas Health Science Center at Houston, Houston, Texas, USA.

Farrah Kheradmand

Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas, 77030, USA.

David B Corry

Department of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston Texas, 77030, USA. Electronic address: dcorry@bcm.edu.

References

PubMed