Forschungszentrum Borstel
Forschungszentrum Borstel

Priority Research Area Asthma and Allergy

Innate Immunity

Projects

The Division of Innate Immunity is interested in questions regarding the activation of the innate immune system and its crosstalk with the adaptive immune system. In detail, we are analyzing the interaction of dendritic cells and airway epithelial enclosed to the area of asthma prevention and initiation.

In the field of asthma prevention we examine the molecular mechanisms of several bacterial cowshed isolates to mediate protection from asthma and allergic inflammation. In different mouse models, we were able to show that the allergy-preventive effect of the investigated bacterial species is based on the activation of divers signaling pathways. In this context, we have evidence that the interplay of the individual bacteria-induced activation patterns can be of importance since exposition to microbial factors with higher diversity correlates with an enhanced allergy protection. Thus, one of our central projects is to investigate if the activation processes caused by the combination of different bacteria species can be an explanation for this finding.

While the immunogenic properties of bacteria as well as their cell components have been extensively studied during the last century, the immunomodulatory potential of archaea has only rarely been investigated. Though the overall morphology of archaea in regard to size and shape resembles that of bacteria, they differ profoundly from them, e.g. regarding the biochemistry of their cell surface structures. During the last decade, the intensive use of modern molecular techniques in microbiome studies revealed that several archaeal species form an essential part of the human microbiota – most probably due to their unique metabolic capabilities. In the last years, we could demonstrate that these mucosa-associated archaeal species specifically interact with components of the human immune system and thus might influence the human immune homeostasis. Hence, in this project, we aim to investigate the molecular cross-talk between mucosa-associated archaeal species (e.g., M. smithii and M. stadtmanae) and human immune (particularly DCs) as well as epithelial cells in order to identify archaea-associated molecular patterns as well as the involved human pattern recognition receptors and activated signaling pathways.

Figure 1

Allergens, e.g. sensitizing substances occur, with few exceptions, throughout all element groups and in different organisms such as plants, fungi, arthropods and mammalians. Further, they can be classified by their functionality for example in enzymes such as proteases, carbohydrases and ribonucleases but they can also be of regulatory function as lipid and iron transporter molecules. One of our further projects is part of the “German Center for Lung Research (DZL)” and addresses the question of how those allergens alone contribute to the modulation of asthma and allergy via direct interaction with the innate immune system. 

Carbon black has become one of the most important industrial carbon products of the last years and is omnipresent due to its use in the synthetics industry, in printers ink, toner and tires. As major component of the so called “fine particulate matter” carbon black nanoparticles (CBNP) are able to penetrate deeply into the lungs and provoke inflammation or enhance existing inflammatory processes. Thus, besides of investigating the direct influence of the particles on lung function and inflammation we analyze how a combination of CBNP and allergens affects those particular processes (toxicity vs. immunogenicity).

In the above-named projects we mainly work in the human system analyzing activation processes in dendritic cells and airway epithelial cells. In the last years the outstanding position of the epithelium became more and more obvious, however, the communication between the airway epithelium and dendritic cells but also mast and T cells is not much understood. Often these analyzes are performed in more and more complex cell culture systems (e.g. 3D Air-liquid interface airway epithelial cell-dendritic cell co-culture), although we are intended to investigate not only activation markers such as the differential gene expression and release of mediators but also direct interaction between the cells via confocal microscopy for instance.

Figure 2

Drosophila

Animal models are of vital importance in lung disease research, and in particular the fruit fly Drosophila melanogaster turned out as an excellent model to elucidate airway specific questions. The respiratory systems of humans and flies - especially in its larval stage - are functionally and physiologically highly comparable. At the same time insect tracheae are simply built organs, thus offers the unique advantage of “whole organism in vivo analyses”. While main innate immune signaling pathways and components are highly conserved, Drosophila lacks all elements of the adaptive immunity. Taken together, these aspects make the fruit fly an excellent and versatile tool to investigate innate immune reactions. Among others our research group is interested in questions regarding basic processes of pathogenesis of the major non-infectious lung diseases: asthma bronchiale, COPD (chronic obstructive pulmonary disease) and lung cancer. Asthma and COPD are chronic inflammatory airway diseases characterized by tissue modifications (remodelling).

Selective manipulation of signaling pathways in larval respiratory epithelial cells, result in structural transformations of the tissue architecture, which correspond with those observed in a severe state of asthma and COPD. These disease models are used to understand genetic and cellular processes responsible for the dramatic tissue modifications (ana-, meta- and hyperplasia) and epithelial inflammatory reactions.

Another project, funded by a grant of the Else-Kröner-Fresenius-Stiftung, is concerned with the modellig of “lung tumors” in the respiratory organs of Drosophila melanogaster. Our aim here is an accurate classification of the basic genetic processes during lung cancer development, to discover new potential therapeutic approaches in a personalized cancer treatment.

Figure 3