Grant: Operating Grant

Neutrophils (also called PMNs) are the most abundant white blood cell in circulation and they patrol in the blood "looking" for infection or injury to tissues. PMNs are critical immune cells that are primarily responsible for protection against bacteria, fungi (molds) and small parasites that invade into the blood or tissue. Upon infection, PMNs are rapidly recruited to the site of infection where they move out of circulation and into the infected tissue. Once at the site of infection, PMNs attack the invading organism and release their contents to initiate a potent inflammatory cascade. Neutrophil contents can directly kill the infecting organism, or recruit other immune cells to help fight the invasion. Unfortunately, inappropriate or continued activation of neutrophils can lead to destruction of host tissue and cause chronic inflammatory disease. In our proposed project, we will study the molecular mechanisms that control how neutrophils become activated and are recruited to sites of inflammation. In addition, we will study how neutrophils can "tune" long term immunity to inflammatory disease. Specifically, we are interested in how a key pathway in neutrophils (the PI3K pathway) regulates these neutrophil functions. To complete these studies, we will use mouse models of asthma and lung inflammation. We have certain strains of mice that have been genetically modified in a way that allows us to manipulate the activation of the PI3K pathway. We can use these mouse models to study how targeting the PI3K pathway (e.g., with specific drugs) can influence neutrophil functions and inflammatory lung disease.