Daniel Calabrese, MD

Cytomegalovirus (CMV) is a common virus that infects up to 90% of the global population and permanently resides in a latent form. Patients with severe lung injury have increased risk for CMV reactivation, and when this occurs, it can lead to death. We have shown that the natural killer (NK) cell is important in constraining CMV infections. However, these cells cause injury after transplant rather than promote lung health. It is unknown how CMV influences this important cell population nor how they cause lung injury together. We believe that special NK cells that can recognize CMV are increased after damage to the lungs. We propose to develop a new system to study how CMV reactivation in the lung influences these NK cells. Success in this project will be critical to understanding how CMV causes lung disease, and how it shapes the lung immune system. Our new methods will identify potential targets to prevent human disease and lung injury.

Update: We developed a new mouse model to study CMV reactivation, where lung injury caused by restricted and then restored blood flow (ischemia-reperfusion) triggered strong CMV reactivation. We also found that lungs with both injury and latent CMV showed more severe damage. Notably, the injury led to a large increase in resident memory NK cells. When NK cells were removed, lung damage decreased and survival improved. Together, these results suggest that CMV and NK cells interact in a way that makes the lungs more vulnerable to injury.