Summary

Candida auris is an emerging fungal pathogen with a remarkable ability to persist on human skin, but how structural skin cells respond to colonization was unclear. Using ex vivo human skin models together with primary keratinocytes and fibroblasts, this study characterizes epithelial and stromal responses to C. auris compared with C. albicans.

C. auris formed biofilms and induced a wound-model-dependent cytokine response dominated by IL-1β and IL-6, yet caused minimal epithelial damage. RNA sequencing revealed complementary, cell-type-specific responses: keratinocytes and fibroblasts both amplified a pro-inflammatory IL-6/CXCL8 response, while keratinocytes additionally upregulated antimicrobial genes such as RNASE7, TSLP, and DEFB103A (human β-defensin 3), alongside neutrophil-recruiting chemokines CXCL2 and CXCL3. Fibroblasts further induced CCL28, supporting T cell recruitment.

Recombinant RNase 7 and short-form TSLP directly inhibited C. auris growth in vitro in a dose-dependent manner, identifying keratinocytes as epithelial sentinels that integrate inflammatory and antimicrobial defenses against skin-tropic C. auris, and pointing to antimicrobial peptides as potential therapeutic targets to limit skin colonization.