Analysis of the skin tissue niche of Trypanosoma cruzi infection

Many chronic diseases are caused by infections that our immune system can't fully eliminate. Instead of completely getting rid of an infection, the immune system controls it, but some of the micro-organisms causing the infection remain in the body at low levels. These persistent infections can slowly lead to severe and sometimes fatal illnesses. Certain areas of the body are particularly susceptible to chronic infections, including the central nervous system and "barrier sites" that are exposed to the outside world such as the lungs, gut and skin. Chagas disease is caused by chronic infection with parasites called trypanosomes (Trypanosoma cruzi). More than 6 million people have T. cruzi infections worldwide and they are at risk of life-threatening diseases affecting the heart and digestive system. By studying T. cruzi infections in laboratory mice we have recently found that the skin is one of the major sites where it is able to persist, yet there are no signs of disease in this tissue. In this project our aim is to find out what is special about the skin tissue and its immune response against T. cruzi that allow this parasite to avoid elimination. To do this we will investigate the precise location of parasites within the complex skin tissue, which is made up of many different structures and cell types. We will also use a variety of cutting-edge experimental techniques combined with computer-based approaches to analyse large amounts of biological data to find out which genes, molecules and cells of the immune system are involved in controlling T. cruzi in the skin. Our hypothesis is that some of these genes, molecules and cells act as "brakes" on the intensity of the immune response, which allows some parasites to survive in order to avoid too much collateral damage to the skin tissue. An improved understanding of how this parasite develops and interacts with the immune system will improve our ability to develop better ways to diagnose and treat infections.