Priority Research Area Chronic Lung Diseases

Projects

The research group Innate Immunity deals with topics regarding the activation of the innate immune system and the resulting crosstalk with the adaptive immune system. In particular, the question of how asthma develops at the cellular level and how this can be prevented will be examined. The focus is on the respiratory epithelium as the first contact zone for aerogenic allergens and dendritic cells as essential activators of the adaptive immune system. The elucidation of the molecular mechanisms that play a role in allergies and asthma serve as a basis for the development of novel approaches in both prevention and therapy.

 

Does the contact with microorganisms protect against allergies? (CONTROL)

On the subject of allergy prevention, we have been investigating the molecular mechanisms by which bacteria isolated from cowsheds provide protection against asthma and allergic inflammatory reactions for several years. We were able to show in various models that the protective effect of the bacteria studied is based on the activation of different cellular pathways (Debarry et al. 2007, Debarry et al. 2010, Hagner et al. 2013, Stein et al., 2017). In this context, the interaction of the individual activation patterns caused by the different bacteria seems to be crucial, as it becomes more and more clear that an increased diversity of microbial exposure is also leading to an increased protection. A central project therefore examines to what extent synergistic or activation processes, which are only triggered by the combination of different bacterial species, can be an explanation for these diversity effect.

While bacteria and their metabolites have been the subject of immunological studies for a long time, research into the immuno-modulatory potential of archaea is not yet very advanced. Although archaea are morphologically very similar to bacteria, they are significantly different from these, for example regarding the biochemical composition of their cell wall. In recent years, microbiome studies have shown that different species of archaea – presumably due to their unique metabolic properties – form an essential component of the human microbiota. We were able to demonstrate that archaea can interact specifically with components of the human immune system and thus have an impact on immune homeostasis (Bang et al. 2014, Bang et al. 2017, Vierbuchen et al. 2017). Therefore, in this project, we are now investigating the molecular basis of the interaction of mucosa-associated methanogens (e.g., the archaeal strains M. smithii and M. stadtmanae) with human immune cells (especially DCs) as well as epithelial cells, in order to identify the involved molecules on the side of the archaea and the activated signaling pathways in human immune cells.

Why do allergens cause allergies and what role do lipids play in this? (CARE)

Allergens occur in all groups of substances with a few exceptions and are present in a wide variety of organisms, such as plants, fungi, limbs or mammals. Functionally, they belong to a wide variety of groups; there are a variety of enzymes such as proteases, carbohydrases and ribonucleases, but also lipid or iron transport molecules and thus they often have a regulatory function. One focus of our research group within the framework of the "German Center for Lung Research (DZL)" is therefore the question to which extent the allergens themselves - by activating the innate immune system - contribute to the development and modulation of allergies and asthma. Furthermore, as part of the flagship project “Basic Science” of the DZL, we investigate how the complex formation of hydrophobic allergens and lipids of an allergen source (e.g. house dust mite and peanut) changes the immune response compared to the allergen itself. In the above-mentioned projects, we mainly work in the human system and study activation processes in dendritic cells and the respiratory epithelium. The importance of the respiratory epithelium has greatly increased in recent years, and many lines of communication between the respiratory epithelium and dendritic cells are not well understood so far. These studies take place in increasingly complex cell culture systems (e.g. 3D air-liquid coculture with respiratory epithelium and dendritic cells), where we not only determine the differential gene expression and the release of mediators, but also want to study the direct interactions between the cells through, for example, confocal microscopy.