Funding outcome

Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are common chronic intestinal (gut) disorders that affect up to 0.5% of the population, especially young children. These diseases are common in developed countries, particularly in Canada. The cause of these complex disorders, while unclear, does suggest a role for gut bacteria. Understanding how microbes contribute to damaging the bowel could guide development of novel therapies. The proposed study looks at an important group of proteins that protect hosts from bacteria, called inflammasomes. We have found that inflammasomes protect mice from developing IBD after infection and are now trying to understand how. The hypothesis of this proposal is that the inflammasome helps immune cells called macrophages eradicate bacteria. In order to assess the importance of the inflammasome, we have developed ways of turning the inflammasome on and off. Ghazal will use these techniques to see how turning the inflammasome on and off affects the ability of the macrophage immune cells to engulf ('swallow') and kill bacteria. She has done this last summer with mouse cells and bacteria, but will now test this with human cells and bacteria, including bacteria isolated from children with IBD. This will be done by infecting macrophages with different bacteria and then looking at what happens through the microscope and counting the cells that are swallowed and then killed by macrophages. Ghazal will use different kinds of bacteria (some can cause disease and some cannot; some from IBD patients and some from healthy children) to see if our immune cells act the same against all bacteria or just those that are causing damage. Although we have effective medications to treat children with IBD, many of them are still sick and we need to better prevent disease and treat patients. These studies will help us understand how our immune system is able to get rid of bacteria and how we might be able to improve this. Since this seems to be not working in IBD, especially in children, finding new ways to improve the ability of immune cells to control bacteria may lead to new treatments and improve the outcomes of pediatric IBD patients.