Alexander Mohapatra, MD, PhD

Tuberculosis remains a leading infectious cause of death worldwide, in part due to the lack of an effective vaccine and the emergence of multi-drug resistant strains. We have shown in mice that an immune cell called the monocyte enters the infected lung from the blood and matures into two different cell types, only one of which kills M. tuberculosis effectively. Consequently, the cells that enable M. tuberculosis survival contain most of the pathogens in the lung. Moreover, these cells are not very accessible to other protective immune cells or current drugs. We will study how monocytes mature in order to develop new therapies that increase production of the cells that can kill M. tuberculosis. These findings will improve the effectiveness of current tuberculosis regimens and shorten treatment times.

Update: Originally, we planned to transfer monocytes from bone marrow; however, we found a simpler method: labeling them in the blood with an antibody that allows us to track them after they enter the lungs. Using this approach, we discovered that monocytes begin changing in less than 24 hours. We used a technique called spectral flow cytometry and newly discovered markers to identify unique monocyte subgroups and understand how these cells respond to infection. We then sorted and analyzed these cells using single-cell RNA sequencing to study their gene activity. This will give us a clearer picture of what happens inside these cells as they change and fight infection. Our work aims to uncover the rapid changes in monocytes during lung infections, which could lead to better treatments for tuberculosis and other diseases.