Grant: Project Grant

One in five Canadians have lung disease and it is estimated that chronic lung diseases cost the Canadian economy about $12 billion. Patients with chronic lung diseases are more susceptible to bacterial infections and with the increased prevalence of antibiotic resistant strains (MRSA) in hospitals, this is an important health concern. Here, we aim to better understand how specific immune cells in the lung normally clear a bacterial infection and how this process is compromised in fibrotic lungs. By performing these studies in mice, we can evaluate the effectiveness of using novel cell-based therapies to prevent fatal lung infections and reduce lung inflammation and fibrosis. This project will examine the function of a particular group of immune cells called monocytes and macrophages that play a dual role in promoting and protecting the lungs from inflammation and damage. By analyzing these cells in normal and fibrotic lungs as well as their ability to respond to infection with MRSA, we will gain new insights into what populations are altered or dysfunctional. To do this we will use a very sophisticated new technology that will allow us obtain considerable new data on their identity and function in the inflammatory response that has previously not been possible. We will then evaluate the potential for macrophage-based therapies to correct or alleviate disease symptoms. We hypothesize that the macrophages that reside in the airways will make the best candidates for anti-bacterial and anti-fibrotic therapy. These macrophages will be isolated from other mice or generated in a culture dish then instilled into mouse lungs and their ability to improve disease outcome assessed. If they do, then we will have made significant progress towards validating the potential for a new kind of cell therapy to treat lung infections and chronic lung disease. Furthermore we will gain significant new knowledge on how monocytes and macrophages regulate lung inflammation and its resolution.