Grant: Project Grant

The lung is exposed to the external environment so we breath in some bacteria and noxious molecules with every breath. Most of these bacteria never reach the little sacs (alveoli) where oxygen is taken up but some bacteria always do. We use a special microscope to image the alveoli of mice and we have uncovered some critical functions of the immune cells. The immune cells that live in these sacs are called alveolar macrophages and they run from alveolus to alveolus through little tunnels between alveoli and vacuum up all bacteria. If the alveolar macrophages cannot crawl between alveoli than problems arise. When you get a viral infection like the flu, then macrophages cannot crawl very well and now bacteria take advantage of the situation and grow in the alveoli causing infection. The lung is surrounded by a really large sac called the pleural space and we have macrophages inside that sac as well that may oversee the role of the alveolar macrophages New macrophages come into the lung and need training to be lung macrophages. This will happen through epigenetic changes ie., environmental changes that affect the way your genes work (not changes in gene sequence though) and this will lead to better vacuuming of bacteria. In other words if our macrophages see a bacterium and have to kill it, through epigenetic changes the macrophages will kill bacteria much better the next time. We think that the more robust the microbiome is and the more we are exposed to environment the better our macrophages will be at vacuuming bacteria. However, this may make our macrophages worse at doing other chores. As mentioned, sometimes noxious stimuli enter the lungs and cause some damage and repair is required. If our macrophages are trained to do that they may not be as good at vacuuming bacteria. We will investigate how these macrophages manage to clear bacteria and repair.