Immunomodulation by IPSE/alpha-1, an excretory/secretory protein from Schistosoma mansoni eggs

• Applicant: Dr. Gabriele Schramm
• Subject Area: Immunology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213413033

Chronic schistosomiasis is characterized by a strong anti-inflammatory immune response caused by schistosome eggs. We have earlier identified a schistosome egg product, IPSE/alpha-1, that triggers basophils to release IL-4 and IL-13. Notably, these cytokines inhibit inflammation by re-ducing pro-inflammatory cytokine release and by inducing anti-inflammatory alternatively activated macrophages (AAMs). Since basophils migrate to parasite-affected tissues and are involved in inducing AAMs, we propose that by triggering basophil IL-4 IPSE/alpha-1 turns down inflammatory processes. Unpublished data from our lab support this hypothesis. Interestingly, the anti-inflammatory effect of IPSE/alpha-1-activated basophils is amplified by TLR ligands. We plan to systematically investigate the effects of IPSE/alpha-1: i) on pro-/anti-inflammatory cytokine release in cell co-culture systems, ii) on immune cells beyond basophils including mediator release and functional consequen-ces, and iii) regarding protection against chronic experimental colitis. We expect our study will help develop new strategies for treating chronic inflammations such as allergy and autoimmune diseases.

• DFG Programme: Research Grants