Project Details
Description
Schistosome parasites infect >200 million people and cause disease in some of the world’s poorest countries. Some infected people eventually become partially resistant to infection, but we do not know how the human immune system kills schistosomes. At the moment, our knowledge of human immunity to these parasites is based almost entirely on blood samples from infected people. How well this reflects immune responses that occur in deeper tissue is not clear.
In this study, we will make a special type of mouse with a human immune system (“humanised mouse”). Humanised mice are exciting tools used to study human immune responses to HIV, tuberculosis and malaria. However, no one has used humanised mice to study schistosome infection. Our aim is to infect humanised mice with schistosomes, to learn how human immune cells respond to, and ultimately kill, these parasites. This knowledge will help us design better treatments to prevent disease.
In this study, we will make a special type of mouse with a human immune system (“humanised mouse”). Humanised mice are exciting tools used to study human immune responses to HIV, tuberculosis and malaria. However, no one has used humanised mice to study schistosome infection. Our aim is to infect humanised mice with schistosomes, to learn how human immune cells respond to, and ultimately kill, these parasites. This knowledge will help us design better treatments to prevent disease.
Key findings
- Very high level of innate and adaptive human immune cell engraftment in humanised NSG SGM mice (including CD4 T cells, CD8 T cells, B cells, macrophages).
- Engrafted human immune cells develop appropriate immune structures in mouse tissues e.g. T cell and B cell areas within the spleen.
- Schistosomes parasites and infect and appropriately develop within humanised mice e.g. maturation into egg-producing adult worms
- Initial experiments suggest spleen Th2 differentiation is low in schistosome-infected humanised mice compared to standard mouse models (i.e. infected C57BL/6).
- We are currently confirming this using human stem cells from different donors and an egg transfer model.
- On-going experiments are assessing the development of egg-induced liver granulomas.
- Engrafted human immune cells develop appropriate immune structures in mouse tissues e.g. T cell and B cell areas within the spleen.
- Schistosomes parasites and infect and appropriately develop within humanised mice e.g. maturation into egg-producing adult worms
- Initial experiments suggest spleen Th2 differentiation is low in schistosome-infected humanised mice compared to standard mouse models (i.e. infected C57BL/6).
- We are currently confirming this using human stem cells from different donors and an egg transfer model.
- On-going experiments are assessing the development of egg-induced liver granulomas.
| Status | Finished |
|---|---|
| Effective start/end date | 1/11/17 → 31/10/18 |