Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. Although both conditions exert a devastating global impact and lack effective vaccines or refined therapeutics, basic knowledge of the key cell types and mediators that control Type 2 immunity and inflammation is currently limited. The focus of this project will be the helminth Schistosoma mansoni, the immune response to which is strongly Type 2 biased and intimately involved in the pathology that accompanies infection. Schistosomiasis is second only to malaria in terms of the number of deaths caused annually by a parasitic disease. However, the key cellular and molecular networks that comprise immunity, inflammation and tissue repair against schistosomes are still unclear.Many helminths undergo part of their lifecycle within barrier sites, where they can physically disrupt tissues by latching on to, burrowing into, or even migrating through them. In the case of S. mansoni, larval parasites migrate through the lungs, liver, and vasculature, while parasite eggs transit from intestinal blood vessels, lodging in and rupturing through tissues. Thus, these parasites have evolved potent strategies to ensure ‘regulated’ inflammation, promoting rapid and effective tissue repair, while limiting dangerous inflammatory damage. The specific aim of this project will be to reveal core immune and inflammatory features of the ‘regulated’ Type 2 mucosal response to S. mansoni, with a focus on defining the role of macrophages, dendritic cells and CD4+ T cells in induction vs. regulation of intestinal and/or pulmonary tissue damage and repair during murine infection with this parasite. Part of this will involve comparing immune cells in tissues vs. those in circulation, and linking immune readouts with sequencing, microbiota and metabolic data sets, to identify key mechanisms that promote or regulate mucosal inflammation against S. mansoni. This project will reveal exciting new information about the core mechanisms involved in coordination of mucosal Type 2 inflammation, which may help future design of innovative therapies and vaccines for both helminth infection and allergies.?The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity