Mechanisms of host:parasite immune regulation during Schistosoma mansoni infection

Schistosomiasis is a widespread and highly debilitating parasitic disease affecting over 220 million people in the poorer countries of the sub-tropical areas and causing the death of an estimated 200,000 individuals every year. Despite its importance, no vaccine is available. Schistosoma parasites enter the human body after contact with infected water and take residency in the bloodstream, where they are constantly exposed to the host immune system. To survive, they have developed sophisticated mechanisms of immune escape that protects them from the host immune system for many years. However, the identity of the proteins used by the parasite to suppress immunity remains unknown. Study of animal models and of patients living in areas where schistosomiasis is endemic suggests that it is possible to build up a protective immunity to the disease over time; however, the parasite proteins that the host immune system targets to confer this protection have not yet been found. The main goal of this research project is to identify the parasite proteins targeted by host antibodies to confer protection from infection as well as the proteins that the parasite uses to subvert its host's immune response. Proteins present on the outer surface of the parasite or secreted by the parasite into its host's bloodstream are believed to be the main actors of both of these functions as they are directly accessible to the host antibodies and can directly interact with its immune cells. Using a large and recent collection of over one hundred recombinant proteins produced in the laboratory, which recapitulate the shape and function of the proteins naturally found at the surface of or secreted by the Schistosoma mansoni parasite, we will perform serological and biochemical studies. We will use sera from both mice and Brazilian individuals who are resistant to S. mansoni infection and expose them to the recombinant parasite proteins to determine whether these resistant individuals produce antibodies against specific parasite proteins compared to individuals who are chronically infected with S. mansoni. We will also use some biochemical techniques to identify which parasite proteins are able to bind to human immune cells and how they interfere with the function of proteins that regulate the immune response to parasite infection. By identifying the parasite proteins targeted by the host immune system in the context of natural resistance to infection and those that play a role in immunoregulation, we hope to reveal new candidates that can be developed into much-needed schistosomiasis vaccine targets against this widespread and highly-morbid parasitic disease.