title: Central Role for Dermal Fibroblasts in Skin Model Protection against Candida albicans.
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.
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kühbacher
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.
authors.forename: Helena
authors.initials: H
authors.lastname: Henkel
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.|Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University of Vienna, Austria.
authors.forename: Philip
authors.initials: P
authors.lastname: Stevens
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.
authors.forename: Christian
authors.initials: C
authors.lastname: Grumaz
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.
authors.forename: Doris
authors.initials: D
authors.lastname: Finkelmeier
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.|Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Burger-Kentischer
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.|Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Sohn
authors.affiliation: Department of Molecular Biotechnology, Fraunhofer Institute for Interfacial Engineering and Biotechnology.|Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rupp
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002460:Cell Line; D020405:Dermis / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D053583:Interleukin-1beta; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008297:Male; D008954:Models, Biological; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2
chemical_list: D053583:Interleukin-1beta; D051195:Toll-Like Receptor 2
keywords: CD4+ T cells; Candida albicans; Toll-like receptor 2 (TLR2); dermal fibroblasts; interleukin 1β (IL-1β)