Mycobacterium tuberculosis is a bacterium that causes the lung disease tuberculosis (TB). Approximately one third of the entire world’s population is infected with TB, and emergence of drug resistant bacteria make it of utmost importance to discover better vaccines, better antibiotics, and to develop a better understanding of how the immune system fights the bacteria – and vice versa.
My PhD thesis focuses on how TB is able to subvert the immune response. TB actually infects white blood cells called macrophages that live inside the lung. TB is able to prevent macrophages from digesting it, so the macrophages sit in the lung while the bacteria live and grow inside of them. Another type of white blood cell called T lymphocyte tries to tell the macrophage to kill the bacteria inside. T cells are able to travel to the lymph node where they become activated, and then move back to the lung to motivate the macrophage. However, the bacteria have developed virulence factors, or things that help them infect and grow better, that can prevent T cells from doing their job. One of these virulence factors is called mannose lipoarabinomannan, or ManLAM. Infected macrophages cough up ManLAM, which can stick on to passing T cells. The T cells then become lethargic and cannot exit the lymph node any more, so they become stuck. This might explain why people who have TB have swollen lymph nodes.
The goal of my research is to identify the ways in which TB can prevent T cells from doing their jobs in order to figure out how we can reverse this process. This video shows the sick macrophage sitting in the lung and the T cells circulating between the lymph node and the lung. The macrophage coughs up ManLAM, represented by post-it notes, which sticks onto the T cells. The T cells then sit in the lymph node and are unable to continue trying to motivate the macrophage to get better.