Tuberculosis (TB) is an infectious disease of the lungs that claims 1.5 million lives every year. For over a century, researchers have been dedicated to finding a way to fight off Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, but have failed to develop a reliable vaccine. The most prominently used, the Bacille Calmette-Guérin (BCG) vaccine, has been shown to be hardly effective in hindering the epidemic, and the antibiotic treatments for tuberculosis tend to be toxic and lead to TB-resistant strains. According to Dr. Maziar Divangahi who does research on developing a better cure, “The antibiotics era is approaching its end; we are in serious trouble with this bug if we don’t investigate an alternative approach.”
The first step to understanding the nature of a possible cure is to understand how the body reacts to TB. The body’s natural first line of defense for fighting off the disease is mobilizing macrophages to kill invasive pathogens. A major weapon of the macrophages are enzymes used to bring down pH levels and cripple bacteria. What makes Mtb able to resist this system is the way that it disarms the macrophages’ ability to kill by releasing substances that counteract these enzymes. Mtb also uses the protein Cpnt to aid the release of a tuberculosis necrotizing toxin (TNT), inducing necrosis, or cell death. An immunity factor (IFT) which binds TNT and inhibits its activity is produced as well, preventing self-poisoning.
Previous efforts to improve the vaccine for tuberculosis have generally been focused on T-cells, one of the primary cells involved in the body’s immune response. Unfortunately, this produced disappointing results in pre-clinical and clinical trials. The research teams led by Dr. Divangahi and geneticist Luis Barreiro of the Université de Montréal used a broader perspective to look into finding a different way to trigger an enhanced innate immune response to attack TB. Recently, Divangahi’s team at the Research Institute of the McGill University Health Centre discovered that when the BCG vaccine is given to mice and has access to the bone marrow, it can reprogram the stem cells in the bone marrow to multiply and generate TB-killing macrophages. Barreiro’s team added to the significance of this finding by pinpointing the activated genetic defensive programs of stems cells and demonstrating how they imprint onto macrophages.
The battle isn’t over yet, and the researchers admit that further research is “clearly required to fully harness the power of stem cells in immunity against infectious diseases.” However, the implications of this study are substantial. According to Dr. Barreiro who is optimistic about the study’s findings, “It’s really about finding different ways to develop better vaccines, ones that will harness the power of macrophages and finally put the body’s innate immune memory to use.”