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Professor Andrew MacDonald & Dr Emma Houlder

Institute: University of Manchester

Understanding larval immune responses to human schistosome infection

Schistosomiasis is a neglected tropical disease that affects over 200 million people and is responsible for the death of as many as 300,000 people per year in sub-Saharan Africa alone.

Schistosome parasites have a complicated life cycle, with aquatic larval stages infecting their human host via the skin, intravascular larval migration and maturation through the lungs, before finally ending up in the liver, where the adult schistosomes produce eggs. Whilst human immune responses to adult schistosome worms and eggs have been relatively well studied, we have little to no understanding of human immune responses to migrating larval stages. Importantly, the lung is a major location where migrating larvae are vulnerable to killing by the host. However, the immune response against lung stage larvae remains poorly defined, even though this knowledge may be critical for effective vaccine or therapy development.

In this project we propose to remedy this, using blood and respiratory samples from individuals infected with schistosomes in a controlled human infection study, at weeks 0-4 post infection when schistosome larvae are present. To extend the relevance of this study we will compare these responses to those seen in natural, chronic infection, in an endemic area - Uganda. Specifically, soluble immune mediators (cytokines and chemokines), as well as immune cells, will be measured in blood and respiratory samples. In addition to transforming fundamental understanding of the immunology of human schistosomiasis, we expect the results of this study will inform future testing of vaccine candidates which have been shown to target larval stages of schistosomes.

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