The development and resolution of inflammation is central to the pathogenesis of numerous human diseases. This is true of bacterial infections, in which host inflammatory responses promote pathogen clearance, as well as inflammatory disorders, such as colitis, in which chronic inflammatory responses drive pathogenesis in local tissue environments. In both cases, a critical mediator of cellular inflammatory responses which drive tissue inflammation is the inflammasome, a multiprotein complex, which leads to the activation of caspase-1 and the cleavage and release of inflammatory mediators, such as IL-1?. To monitor cellular inflammatory responses in vivo, we have developed caspase-1 biosensors that allow the detection of inflammatory responses in the context of mouse models of bacterial infection (S. aureus) and colitis. In this application, we propose to develop mice expressing this novel biosensor in a tissue specific fashion. This mouse model will allow us to define the cell types driving inflammation in the context of these established disease models as well as develop an animal model which will be a valuable tool to monitor tissue specific inflammatory responses in the context of numerous mouse models of human disease.
Inflammation is central to numerous human diseases. The ability to monitor inflammation in animal models of human disease is limited and typically requires the sacrifice of the animal. We have developed a novel biosensor to monitor inflammation in live animals. We propose to develop second generation mice which express this biosensor in a tissue specific fashion. This will allow a better understanding of what cell types drive inflammatory responses in the context of bacterial infection and colitis and also establish a mouse line which can be translated to the study of numerous other diseases.
