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.

真菌性气道感染（气道真菌病）是哮喘等过敏性气道疾病的重要病因，但真菌引发哮喘反应的机制却知之甚少。在这里，我们利用野生型和突变型白色念珠菌来确定这种常见真菌如何在小鼠中引发特征性的 Th2 和 Th17 细胞依赖性过敏性气道疾病。我们证明，作为霉菌必需毒力因子的蛋白酶不是白色念珠菌相反，通过肽毒素假丝酵母菌素促进了过敏性气道疾病。念珠菌溶血素通过血管性血友病因子 (VWF) 受体 GP1bα 激活血小板，释放 Wnt 拮抗剂 Dickkopf-1 (Dkk-1)，从而驱动与肺部真菌负荷降低相关的 Th2 和 Th17 细胞反应。血小板同时排除了由真菌肺部侵入引起的致死性肺出血。因此，除了止血之外，血小板还通过涉及念珠菌溶血素、GP1bα 和 Dkk-1 的抗真菌途径促进对白色念珠菌气道真菌病的保护，促进 Th2 和 Th17 反应。