Single-Cell Transcriptomics Unveils Skin Cell Specific Antifungal Immune Responses and IL-1Ra- IL-1R Immune Evasion Strategies of Emerging Fungal Pathogen .

is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue, yet the host immune factors that regulate the skin colonization of are unknown. In this study, we employed unbiased single-cell transcriptomics of murine skin infected with to understand the cell type-specific immune response to skin infection results in the accumulation of immune cells such as neutrophils, inflammatory monocytes, macrophages, dendritic cells, T cells, and NK cells at the site of infection. We identified fibroblasts as a major non-immune cell accumulated in the infected skin tissue. The comprehensive single-cell profiling revealed the transcriptomic signatures in cytokines, chemokines, host receptors (TLRs, C-type lectin receptors, NOD receptors), antimicrobial peptides, and immune signaling pathways in individual immune and non-immune cells during skin infection. Our analysis revealed that infection upregulates the expression of the IL-1RN gene (encoding IL-1R antagonist protein) in different cell types. We found IL-1Ra produced by macrophages during skin infection decreases the killing activity of neutrophils. Furthermore, uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense. Collectively, our single-cell RNA seq profiling identified the transcriptomic signatures in immune and non-immune cells during skin infection. Our results demonstrate the IL-1Ra and IL-1R-mediated immune evasion mechanisms employed by to persist in the skin. These results enhance our understanding of host defense and immune evasion mechanisms during skin infection and identify potential targets for novel antifungal therapeutics.

PMID: 39463935