The study shows that a toxin made by the fungus Candida albicans, called candidalysin, triggers mast cells in the skin to release inflammatory signals. This activation depends on a receptor called dectin-1 and downstream MAPK pathways. In people with candidiasis, both candidalysin and the antimicrobial peptide LL-37 are found near mast cells.

Although mast cells (MCs) modulate the activity of effector cells during Candida albicans infection, their role in the pathogenesis of candidiasis remains unclear. Candidalysin, a C. albicans-derived peptide toxin, is a crucial factor in fungal infections. We aimed to investigate the effect of candidalysin on MC activation and the underlying molecular mechanism. Serum from candidalysin-immunized mice was used to measure candidalysin expression in patients infected with C. albicans. MC degranulation and migration were evaluated by β-hexosaminidase release assay and chemotaxis assay, respectively. EIA and ELISA were used to evaluate the production of eicosanoids and cytokines/chemokines, respectively. The production of nitric oxide (NO) was measured with a DAF-FM diacetate kit, while reactive oxygen species (ROS) production was analyzed by flow cytometry. MAPK activation was evaluated by Western blotting. We detected high candidalysin expression in the lesions of patients infected with C. albicans, and the MC number was increased in these lesions. LL-37 colocalized with MCs in the lesions of candidiasis patients. Candidalysin-enhanced MC accumulation in mice and treating LAD2 and HMC-1 cells with candidalysin induced their degranulation, migration, and production of pro- and anti-inflammatory cytokines/chemokines, eicosanoids, ROS, NO, and LL-37. Interestingly, C. albicans strains lacking candidalysin failed to induce MC activation. Moreover, candidalysin increased dectin-1 expression, and the inhibition of dectin-1 decreased MC activation. Downstream dectin-1 signaling involved the MAPK pathways. The finding that candidalysin causes cutaneous MC activation may improve our understanding of the role of MCs in the pathology of cutaneous C. albicans infection.