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Central Role for Dermal Fibroblasts in Skin Model Protection against Candida albicans
Andreas Kühbacher1, Helena Henkel1, Philip Stevens1,2
1Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.
Abstract:
The fungal pathogen Candida albicans colonizes basically all human epithelial surfaces, including the skin. Under certain conditions, such as immunosuppression, invasion of the epithelia occurs. Not much is known about defense mechanisms against C. albicans in subepithelial layers such as the dermis. Using immune cell-supplemented 3D skin models we defined a new role for fibroblasts in the dermis and identified a minimal set of cell types for skin protection against C. albicans invasion. Dual RNA sequencing of individual host cell populations and C. albicans revealed that dermal invasion is directly impeded by dermal fibroblasts. They are able to integrate signals from the pathogen and CD4+ T cells and shift toward an antimicrobial phenotype with broad specificity that is dependent on Toll-like receptor 2 and interleukin 1β. These results highlight a central function of dermal fibroblasts for skin protection, opening new possibilities for treatment of infectious diseases.
Insights
Dermal fibroblasts protect skin from Candida albicans invasion by integrating pathogen and immune signals. This discovery reveals a key defense mechanism and potential new treatments for fungal skin infections.
Area of Science:
- Immunology
- Dermatology
- Mycology
Background:
- Candida albicans is a fungal pathogen that colonizes human epithelial surfaces.
- Skin invasion by C. albicans can occur under immunosuppression.
- Subepithelial defense mechanisms against C. albicans are not well understood.
Purpose of the Study:
- To investigate the role of dermal cells in skin defense against C. albicans.
- To identify key cell types involved in preventing C. albicans invasion.
- To elucidate the molecular mechanisms underlying dermal fibroblast antimicrobial activity.
Main Methods:
- Development of immune cell-supplemented 3D skin models.
- Dual RNA sequencing of host cells and C. albicans.
- Analysis of fibroblast response to pathogen and CD4+ T cell signals.
Main Results:
- Dermal fibroblasts impede direct dermal invasion by C. albicans.
- Fibroblasts integrate signals from C. albicans and CD4+ T cells.
- Fibroblast antimicrobial phenotype is dependent on Toll-like receptor 2 and interleukin 1β.
Conclusions:
- Dermal fibroblasts play a central role in skin protection against C. albicans.
- Fibroblasts exhibit a broad-specificity antimicrobial phenotype.
- Findings open new therapeutic avenues for infectious skin diseases.