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 GP1ba 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, GP1ba, and Dkk-1 that promotes Th2 and Th17 responses.

Automated summary

Research shows that Candida albicans activates platelets through the peptide toxin candidalysin to release the Wnt antagonist Dickkopf-1, promoting Th2 and Th17 cell responses, reducing lung fungal burdens, and preventing lethal pulmonary hemorrhage resulting from fungal lung invasion.