The immunomodulatory properties of nematode secreted components can spill over to unrelated inflammatory diseases and thereby suppress, for example, autoimmune and allergic diseases. Secreted products of the worms are therefore key for immune intervention by the parasites (Schnöller et al. 2008, Daniłowicz-Luebert et al. 2013, Whelan et al. 2014, Ebner et al. 2014, Ziegler et al. 2015). Our aim is to use these key immunoregulatory components of the nematodes for potentially tackling chronic inflammatory diseases. Hereby we focus on the pig as a large animal model with an intestinal physiology similar to humans to validate the immunomodulatory filarial cystatin (AvCys) as a novel medical product for human inflammatory bowel disease (IBD, figure).
- Ziegler, T., S. Rausch, S. Steinfelder, C. Klotz, M.R. Hepworth, A. Kühl, P-C- Burda, R. Lucius, S. Hartmann. 2015. A novel regulatory macrophage (Mreg) induced by a helminth molecule instructs IL-10 in CD4+ T-cells and protects against mucosal inflammation, J. Immunology, 194:1555-1564.
- Whelan, R., S. Rausch, F. Ebner, J. Richter, N. Hering, D. Günzel, J.-D. Schulzke, A. Kühl, P. Janczyk, K. Nöckler, L. Wieler, S. Hartmann. 2014. A novel therapy via a transgenic probiotic secreting a parasite immunomodulator for site-directed treatment of gut inflammation. Molecular Therapy, 22:1730-1740.
- Ebner, F., M. R. Hepworth, S. Rausch, K. Janek, A. Niewienda, A. Kühl, P. Henklein, R. Lucius, E. Hamelmann, S. Hartmann. 2014. Therapeutic potential of larval excretory, secretory proteins of the pig whipworm Trichuris suis in allergic disease. Allergy, 69:1489-1497.
- Daniłowicz-Luebert, E., S. Steinfelder, A. Kühl, G. Drozdenko, R. Lucius, M. Worm, E. Hamelmann, S. Hartmann. 2013. A nematode immunomodulator inhibits grass pollen-specific allergic responses by controlling excessive Th2 inflammation. Int. J. Parasitol., 43:201-210.
- Schnöller, C., S. Rausch, S. Pillai, A. Avagyan, B. Wittig, C. Loddenkemper, A. Hamann, E. Hamelmann, R. Lucius, S. Hartmann. 2008. A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. J. Immunol., 180: 4265-4272.
Associated scientists: Dr. Lydia Tedin, Lisa Käbisch, Katja Balster, Dr. Sebastian Rausch.
Third-party funds: BMBF VIP+ Programm, Projekt ValNemCys.