Understanding_the_host_immune_response_to_Schistosoma_infection. Understanding_the_host_immune_response_to_Schistosoma_infection

This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ The immune response to Schistosoma mansoni infection in the mouse model is characterised by an initial Th1 response as the parasite penetrates the skin, migrates via the lungs and then matures in the hepatic portal vein. As eggs begin to deposit in the intestines, liver and other tissues, this Th1-dominated response is replaced by a strong acute Th2 response, which is subsequently modulated to a produce a sustained, chronic Th2 response. This immune response to antigens secreted by schistosome eggs leads to the formation of granulomas in tissue - particularly the liver - and thus to the pathology of the disease. There are some unusual features of the immune response to chronic parasitic infections such as Schistosoma, and the balance of different T-cell types in this response, and their activation phenotypes are unclear. We plan two experiments to investigate how RNA-seq transcriptomics can shed light on these processes. First, a detailed time-course of RNA-seq from liver samples from infected and naïve mice, to investigate how global transcription patterns change in liver (the main effector site) at the peak of acute Th2 activity and during the chronic response. Using these data to identify suitable time-points, we then plan to use RNA-seq to investigate T-cell activation in liver and mesenteric lymph nodes (the relevant priming site) using flow-sorted subsets of naïve and activated (CD44low vs CD44high) T-cells producing IL4 and IL13 from IL-4/IL-13 reporter mice. This should give fundamentally novel data about the transcriptional activation status of recently activated and chronically stimulated T cells, which is of great relevance in understanding the immunopathology of long-lived parasitic infections.