Signals for regulatory B cell activation in helminth infection and their application in experimental allergic asthma therapy

• Antragstellerin: Dr. Simone Häberlein
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2013 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 234413401

High-income countries are facing an increased prevalence of hyperinflammatory disorders, such as allergies. Emerging evidence suggests that infection with helminths induces regulatory immune cells that strongly suppress allergic inflammation. This immune-downmodulating activity not only ensures parasite survival but may also induce spillover suppression to third party antigens, such as allergens. In particular infections with the helminth Schistosoma mansoni, causative agent of schistosomiasis, were associated with reduced allergies in mice or humans. The group of Prof. Dr. M. Yazdanbakhsh has recently demonstrated that Schistosoma-induced regulatory B (Breg) cells of the splenic marginal zone (MZ) strongly suppress allergic airway inflammation in a mouse model by release of interleukin-10. Therefore, it is of high therapeutic interest to study the conditions in which Breg cells are induced in order to artificially boost their activity as a novel therapy against allergic diseases. Since MZ B cells respond only poorly to direct exposure to schistosomal molecules, I hypothesize that MZ Breg cells instead need activation signals derived from other accessory cells that are well equipped to respond to schistosome molecules. The following objectives will be addressed: (1) the role of MZ macrophage subsets, dendritic cells and stromal cells for Breg cell induction in experimental S. mansoni infection, and (2) the mechanisms involved in this process (soluble factors, receptors). To test the relevance of the identified signals for the human system, I will (3) determine the capacity of monocyte-derived macrophages and dendritic cells from Gabonese schistosome-infected patients to induce Breg cells. As important proof of principle, I will test the therapeutic potential of the identified signals to boost Breg activity in an allergic asthma model. The results from this project can pave the way for the development of novel therapies to enhance Breg activity in allergic diseases.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Niederlande
• Gastgeberinnen: Professorin Dr. Hermelijn Smits; Professorin Maria Yazdanbakhsh, Ph.D.