This complex initial situation was the reason for the development of 3D infection models of the skin, which, in addition to the epithelial cells (keratinocytes), contain structural components such as dermal fibroblasts and collagen as well as immunologically relevant components such as different immune cell types. Such models have already been used to investigate mechanisms of host-pathogen-interactions. So far, especially infection processes in yeast (Candida spp.) as well as viruses (Herpes simplex-virus, HSV-1), and the immune response to these pathogens have been analyzed.
Using genome-wide analysis methods such as next-generation-sequence analyses, these infection models loaded with immune cells can be comprehensively analyzed. It was shown that no individual cell type alone effectively fights a pathogen, in this case C. albicans. Cytokine-mediated communication between the different cell types is necessary to launch an effective antimicrobial response by the dermal fibroblasts in the model. One of the key molecules is the immune receptor TLR2 that is necessary to recognize pathogens. It induces a signal cascade, which ultimately stops the yeast invasion.
These results underline the role of immune receptors as important sensors and regulators of the immune system. They help the body decide when and how to activate its immune mechanisms. Therefore, these models are optimally suited to identify and validate immunomodulatory substances that fight infections as well as immunologic diseases. For example, immune-activating substances can quickly eradicate an infection and immune suppressing components can reduce an excessive inflammatory reaction.
Using this strategy, the body’s arsenal against pathogens can be more strongly incorporated in therapeutic approaches. This would lead to quicker recovery from and better protection against infections.
These promising approaches to construct partially immune competent in vitro models will be expanded to better understand the molecular mechanisms of the body’s immune system on the epithelial level. Based on this, new drugs for treating infectious diseases will be developed. This is especially relevant for immune suppressed patients, whose immune system is weakened.