TGF-beta activation by gut dendritic cells: identifying a critical pathway in regulation of chronic parasitic infection

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Our immune system functions to detect and destroy harmful pathogens that enter the body. Upon infection, immune responses are rapidly activated, to ensure the threat is dealt with as quickly as possible. However, pathogens known as helminth parasites can hijack the immune system to suppress responses aimed at eliminating the infection, therefore allowing the pathogen to live and breed inside the body. These so-called chronic helminth infections are major world health problems, with over one quarter of the world population affected, mostly in developing countries. Infections with helminth parasites cause major health and economic problems, but at present treatments for the infections are extremely limited. A vital area of scientific research therefore aims to understand how helminths control immune responses to allow their survival inside our body. Such work will therefore lead to the identification of potential novel therapeutic targets for treating chronic helminth infection.Our new exciting data has identified important molecules that are critically involved in the development of chronic helminth infection. Hence, when cells of the immune system called dendritic cells have reduced ability to activate an important molecule called TGFbeta, chronic infection cannot develop in a mouse model of an important human gut helminth infection. However, why protection from chronic infection occurs is completely unknown. The work proposed here aims to uncover why lack of a specific pathway in the immune system causes complete protection from chronic infection in the gut, determining the cells and molecules of the immune system involved in such protection. We will also determine whether such resistance from infection is seen for other types of parasites, or whether protection is specific to helminth parasites that infect the gut. Our work will therefore provide important insights into immune molecules, cells and mechanisms that are involved in allowing parasites to develop chronic infection, thus identifying potential novel therapeutic targets for treatment of these devastating diseases.