Characterization of the T helper 17 response to the fungal commensal Candida albicans in health and disease
T helper 17 (Th17) cells enhance the barrier function of mucosal epithelial surfaces exposed to various microbes. However, their aberrant activation is associated with inflammatory diseases. Candida albicans, a fungal commensal that colonizes skin and mucosal surfaces, is a major inducer of human Th17 cells. The mechanisms behind the host-fungal interaction leading to Th17 induction are not fully understood. We characterized the human CD4+ T cell response to C. albicans in healthy individuals and patients with skin and gut inflammatory diseases, where aberrant Th17 responses are implicated in pathogenesis. Using the antigen reactive T cell enrichment (ARTE) assay, we identified C. albicans proteins, including SUN41 and HYR1, as major targets of the Th17 response in healthy individuals. These major target proteins, enriched in extracellular vesicles (EVs) from C. albicans, showed low homology to proteins from related Candida species, highlighting C. albicans' unique ability to activate Th17 cells. C. albicans-specific Th17 produced IL-17A, IL-22, IL-21, GM-CSF, and the skin-homing marker CLA. We found C. albicans-specific T cells in the skin, with skin-derived APCs secreting Th17 priming cytokines in response to C. albicans, suggesting that the skin is an important priming site for C. albicans-specific Th17 cells. We also observed alterations in C. albicans-specific T cell responses in patients with Bullous Pemphigoid (BP) and Crohn’s Disease (CD). BP patients showed increased IL-17A and IL-21 levels in response to major targets, while CD patients exhibited two distinct C. albicans-specific T cell phenotypes. In summary, our findings highlight the complex T cell response to C. albicans in health and disease across various anatomical sites.
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