Activated Signalling Cascades of Innate Immunity Predicting the Onset of Type 1 Diabetes

The mammalian immune system has evolved in constant contact with microbes. Some microbes can be beneficial for the host; however, the primary pathogens or commensal, opportunistic microbes can cause infectious diseases if they overcome the protective host responses.

The active immune system, consisting of innate and adaptive immunity, is directed to protect the host from infection by eliminating the intruding pathogens and by taking care of damaged structures. At the same time, immune system must control the activated immune response; uncontrolled or miscontrolled immune response may lead to autoimmune diseases, other types of acute or chronic inflammatory diseases, or unordinary severe infection diseases. Thus, as a first-line of host defence, innate immunity has a central role at the onset of infection, in particular, for newborns and in early childhood, when the adaptive immunity is still imperfectly developed. The most recent studies suggest that innate immunity may have role in the early events in the pathogenesis of type 1 diabetes.

Our aim is to clarify how the activation of innate immunity is engaged to the onset of diabetes-associated autoimmune process and to development of clinical type 1 diabetes. Our specific aim is to study the activation of innate immunity receptors, especially toll-like receptor (TLR) signalling cascades and the clinical importance of this activation in type 1 diabetes development. We will determine whether activation mechanisms of innate immunity against virus and bacterial infections and other surrounding pathogens are miscontrolled in children with genetic type 1 diabetes susceptibility. The results gained from this study will provide new information of the mechanisms and environmental factors that influence to the onset of the disease in genetically susceptible individuals.