Understanding the host immune response to Clostridium difficile infection

Clostridium difficile is recognised as the major cause of nosocomial diarrhoea in Australian hospitals and in hospitals worldwide. Chronic colitis syndromes caused by this organism are a significant cause of morbidity in hospitals with control and treatment costs rapidly escalating. The recent emergence of hypervirulent strains has increased the severity of disease and hence the urgency with which the mechanism of disease needs to be understood. The pathogenesis of C. difficile-associated diseases involves the production of numerous toxins and other virulence factors. We have developed a mouse model of infection which closely mimics human infection. This project will use the mouse model of C. difficile infection to assess the host immune response to C. difficile infection, in particular using specific mutants of clinically relevant C. difficile strains. Our primary focus will be on the ability of C. difficile toxins to modulate specific immune responses during disease and we will extend these studies into a broader exploration of the pathways involved downstream of these responses, including the effect of C. difficile infection on repair capacity of the gut and stem cells.