Project 12
Ursula Wiedermann, Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna.
Project 12: Parasite-derived adjuvants for prevention and therapy of allergy
Ursula Wiedermann has long experience and expertise in experimental work with different mouse models for allergy and infectious diseases with a special focus on mucosal immunology and vaccinology. Within recent years she established mouse models of polysensitization to develop new prevention and treatment strategies against allergic co-sensitization. Based on the finding that infection with certain parasites can suppress allergic immune responses, she now plans to identify the factors and acting mechanisms responsible for parasite-derived allergy suppression and develop vaccination approaches utilizing pathogen-derived adjuvants. Previously Wiedermann has demonstrated that infection with the ubiquitous parasite Toxoplasma gondii prevented allergic immune responses and airway inflammation in a mouse model of birch pollen allergy. Since the recent studies suggest that immunosuppression can also be induced by inactivated parasites, she plans to evaluate if T. gondii extracts and defined compounds down-regulate allergic polysensitization when co-applied with allergen-chimers. The role of regulatory cells (T and B cells, DCs or myeloid-suppressor cells) in preventing/reducing allergic polysensitization will be investigated in the mouse model as well as in a human in vitro system using cells from allergic and healthy donors.
Based on increasing evidence that early life exposure to certain microbes play an important role in immune programming to prevent allergy development, it will be studied if T. gondii-derived compounds facilitate immunomodulation when applied during the pre-and perinatal period. Additionally it will be evaluated if epigenetic activation/silencing of immune-related genes (e.g. DNA methylation/demethylation of selected target genes) account for prenatal immunomodulation by parasite derived compounds.
The proposed studies shall help to identify new immunomodulatory parasite-derived adjuvants for allergy vaccines and elucidate their mode of action. Further they may clarify, whether early intervention with such adjuvants can lead to immuno-programming towards a non-allergic immune status, thereby offering a potent prevention strategy against allergic diseases.
Publications:
Schabussova I, K. Hufnagl, ML.Tang, E. Hoflehner, A. Wagner, G.Loupal, S. Nutten, A.Zuercher, A.Mercenierand, U. Wiedermann. 2012. Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy. PLoS One. 2012;7(7):e40271. doi: 10.1371/journal.pone.0040271.
Hoflehner E, K. Hufnagl, I. Schabussova, J.Jasinska, K. Hoffmann-Sommergruber, B. Bohle, RM.Maizelsand, U. Wiedermann. 2012. Prevention of birch pollen-related food allergy by mucosal treatment with multi-allergen-chimers in mice. PLoS One. 2012;7(6):e39409. doi: 10.1371/journal.pone.0039409.
Schabussova I, K.Hufnagl, C.Wild, S.Nutten, AW.Zuercher, A.Mercenierand, U. Wiedermann. 2011. Distinctive anti-allergy properties of two probiotic bacterial strains in a mouse model of allergic poly-sensitization.Vaccine. 2011 Feb 24;29(10):1981-90. doi: 10.1016/j.vaccine.2010.12.101.
Schwarzer M, A.Repa, C. Daniel, I. Schabussova, T.Hrncir, B. Pot, R.Stepankova, T.Hudcovic, A. Pollak, H.Tlaskalova-Hogenova, U. Wiedermann and H.Kozakova. 2011. Neonatal colonization of mice with Lactobacillus plantarum producing the aeroallergen Bet v 1 biases towards Th1 and T-regulatory responses upon systemic sensitization. Allergy. 2011 Mar;66(3):36875. doi: 10.1111/j.1398-9995.2010.02488.x.
Wagner A, E. Förster-Waldl, E. Garner-Spitzer, I.Schabussova, M. Kundi, A. Pollak, O.Scheiner, A.Joachimand, U.Wiedermann. 2009. Immunoregulation by Toxoplasma gondii infection prevents allergic immune responses in mice. Int J Parasitol. 2009 Mar;39(4):465-72. doi: 10.1016/j.ijpara.2008.09.003.