The host protective role of IL-4R alpha responsive T cells and macrophages against schistosomiasis. (360G-Wellcome-080921_Z_06_Z)

The Interleukin's IL-4 and IL-13 are the major cytokines needed for protection during murine schistosomiasis, an experimental model for the human disease, also known as bilharzia. IL-4 receptor alpha (IL-4Ra) deficient mice are impaired in IL-4 and IL-13-mediated responsiveness, therefore highly susceptible to S. mansoni infection and succumb during acute schistosomiasis. The recent generation of cell type specific IL-4Ra deficient mouse strains in my laboratory, allowed to uncover and dissect the role of IL-4/IL-13 dependent and independent target cells in comparative infection studies. Here, we were able to demonstrate data suggesting a protective role of IL-4-independent T helper 2 (TH2) and regulatory T cells (Treg), IL-4/IL-13-activated alternative macrophages (aaMph), as well as their immunomodulatory cytokines, TGF-b and IL-10 during acute schistosomiasis. The aim of this project is to further characterise and dissect the role of these 'players' in host protective mechanisms against murine schistosomiasis. Key goals include:1) The characterisation and identification of genes relevant for host protection from Schistosoma-induced TH2 cells and aaMph's using gene expression profiling. 2) The identification of the mode of action by aaMph's and Treg's in preventing deleterious gut pathology.3) The role of TGF-b and IL-10 in immunomodulation in relation to IL-4/IL-13 responsiveness during schistosomiasis.