Grant: Operating Grant

The lung directly contacts the environment via a huge collection of air-filled sacs called alveoli. The disadvantage of this interaction is the constant exposure of the host airways to airborne pathogens. As well, the lung alveoli are richly supplied with blood, which results in a massive surface area of blood vessels in close proximity to potential pathogen portals of entry. Certainly, microbial pathogens can penetrate from the lung alveoli into the circulation and rapidly disseminate to other vascular beds and tissues. Bacteremia, or bacteria that has entered the blood stream, has important clinical implications as affected patients require longer courses of intravenous antibiotics, longer hospital stays and have higher mortality rates. Being at the forefront of pathogen interactions, the lung plays a critical role in containing pathogens before they spread, however it remains unclear if, and how, the lung deals with microbes that breakthrough the barrier and make it to the blood circulation. The overarching hypothesis of this grant proposal is that pre-positioned lung neutrophils in the blood vessels act as vascular sentries by performing surveillance and capture of any blood-borne bacteria. We are utilizing state-of-the-art microscopy for intravital lung imaging, which allows for greater cellular and molecular resolution of pulmonary intravascular immunity, in live animals, in real time. Understanding the role that lung neutrophils play in protecting us from harmful pathogen entry into the blood will allow rational therapeutic design to enhance this process in severely infected humans.