Canadian researchers report that they can reprogram hematopoietic stem cells to kill tuberculosis (TB). Their research was published yesterday in Cell.
Maziar Divangahi, a pulmonary immunologist at the Research Institute of the McGill University Health Centre, and Université de Montréal geneticist Luis Barreiro led the research. Together they were able to show that when Bacillus Calmette–Guérin (BCG), a TB vaccine, is administered to mice in a way that enables access to the bone marrow, it can reprogram stem cells.
The innate system, via stem cells in the bone marrow, mobilizes macrophages that swallow and kill invading bacteria like Mycobacterium tuberculosis (Mtb). However, Mtb disarms the killing program of macrophages and uses them as a kind of "sanctuary" to replicate and grow. Determined to boost the TB-killing efficiency of macrophages, Dr. Divangahi's and his team vaccinated mice with BCG and in a series of experiments observed that in the bone marrow BCG was able to reprogram the stem cells to proliferate and generate TB-slaying macrophages.
"Although we demonstrated that BCG educates stem cells to generate trained immunity, we had no idea about the molecular mechanisms that were involved in this protective pathway," says Dr. Divangahi. To find out what those molecular mechanisms were, the team examined the genomic pathways involved in triggering the enhanced innate immune response against TB.
Dr. Barreiro's team demonstrated how the protective programs were imprinted and transmitted from stem cells all the way to macrophages. In addition, they identified the genetic imprint of the protective pathways in educated macrophages that were "turned on" to kill the TB pathogen. "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," says Dr. Barreiro.