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- Title
Candidalysin, a Virulence Factor of Candida albicans, Stimulates Mast Cells by Mediating Cross-Talk Between Signaling Pathways Activated by the Dectin-1 Receptor and MAPKs.
- Authors
Song, Pu; Peng, Ge; Yue, Hainan; Ogawa, Takasuke; Ikeda, Shigaku; Okumura, Ko; Ogawa, Hideoki; Niyonsaba, François
- Abstract
Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects
MAST cells; CANDIDA albicans; CANDIDA; CELLULAR signal transduction; MYCOSES; PEPTIDES; ECHINOCANDINS; TRYPTASE
- Publication
Journal of Clinical Immunology, 2022, Vol 42, Issue 5, p1009
- ISSN
0271-9142
- Publication type
Article
- DOI
10.1007/s10875-022-01267-9