ImResFun – Identification of protective mechanisms of the skin using immunological 3D tissue models

The human skin forms an important barrier against microorganisms such as the human pathogenic fungal yeast Candida albicans. 3D tissue models offer significant advantages in the analysis of mechanisms of host-pathogen interactions, which are important during adhesion and invasion of the pathogen. They reflect the natural infection environment much better than classical 2D cell cultures.

ImResFun.
ImResFun.
Infection of skin models with C. albicans in the presence (right) and absence (left) of immune cells.
© Fraunhofer IGB
Infection of skin models with C. albicans in the presence (right) and absence (left) of immune cells.

By integrating human immune cells into a 3D skin model, we developed a test system that allows the analysis of defense mechanisms against invading pathogens [1]. With this tissue model and using gene expression analyses of individual cell types via next-generation sequencing, we have already identified dermal fibroblasts as a cell type that plays a significant role in the protection of the skin against C. albicans invasion.

Due to its properties, the skin model allows comprehensive, cell-type-specific molecular and functional analyses. These showed that in particular the innate immune receptor TLR2 and the messenger substance Interleukin-1β play a crucial role in putting fibroblasts into an antimicrobial status or triggering an antimicrobial response, depending on the presence of an acute fungal infection and of CD4 T-cells [2].

In future, we will expand these studies to other pathogens and epithelia in order to obtain comprehensive information on epithelial barrier functions. This will open up new possibilities for the treatment of infectious and immune diseases by targeted manipulation of specific signaling pathways using immune modulators.

Procedure for the investigation of Candida infections in immunosupplemented skin models.
© Fraunhofer IGB
Procedure for the investigation of Candida infections in immunosupplemented skin models.

Project information

Project title

ImResFun – Molecular Mechanisms of Human Fungal Pathogen Host Interaction

Project duration

October 2013 – September 2017

 

Funding

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 606786.

Literature

[1] Kühbacher, A.; Sohn, K.; Burger-Kentischer, A.; Rupp, S. (2017) Immune cell supplemented human skin model for studying fungal infections, Methods Mol Biol 1508: 439-449

[2] Kühbacher, A.; Henkel, H.; Stevens, P.; Grumaz, C.; Finkelmeier, D.; Burger-Kentischer, A.; Sohn, K.; Rupp, S. (2017) Central role of dermal fibroblasts in skin model protection against C. albicans invasion, J Infect Dis 215(11): 1742-1752