Unravelling the in vivo immune response against Schistosoma mansoni eggs (360G-Wellcome-099784_Z_12_Z)

Schistosomiasis is the second-most socioeconomically devastating parasitic disease. After infection, Schistosoma mansoni eggs become trapped in the smallintestine and the liver. These eggs drive a chronic immune response that generates fibrosis, causing a debilitating and eventually fatal loss of organ function. Drugs to reduce this inflammation are not available, and much remains to be learned about this pathogenic immune response against S. mansonieggs in vivo. Here we propose a detailed analysis of the soluble and cellular mediators thatinduce responses to S. mansoni eggs in the small intestine and the liver of mice in vivo. We will use novel tools to generate heretofore-unavailable insights into these mechanisms. These include recently developed flow cytometric analyses of immune cell populations, cell sorting, genetically modified mouse strains, and cutting-edge in vivo techniques. We aim to identify the specific cells that drive pathogenic responses to S. mansoni, andthe precise cellular sources of the soluble mediators that control this response. Our results will not only produce a detailed understanding of the cellular interactions between immune cells that respond to S. mansoni eggs, transferable to other parasitic infections or even allergic responses, but mayalso present targets for the specific immunosuppression of Schistosomiasis.