Most healthy people can defend themselves against Mycobacterium tuberculosis, but they need all parts of their immune system to work together. A study published in PLOS Pathogens reveals how a special class of immune cells called invariant natural killer T (iNKT) helps to make sure all parts of the immune system are working together to fight the infection.
The findings are based on the results to two studies conducted at the University of Massachusetts Medical School, and headed by Samuel Behar, senior author. According to Behar, the team was interested in identifying the mechanisms that different types of T cells use to control Mycobacterium tuberculosis infection.
As reported by Science Daily, Behar and his team revealed in a previous study that when iNKT cells encounter infected macrophages – the human target cells of Mycobacterium tuberculosis, or Mtb – the iNKT cells somehow prevented Mtb from growing and multiplying inside the macrophages. In the recent study, Behar focused on how the iNKT cells achieved this.
Using a number of cell culture systems and experiments in mice to dissect the interaction, researchers found that when iNKT cells are confronted with Mtb-infected macrophages, they produce and release interferon gamma, a broad-spectrum immune system activator. However, when the scientists blocked interferon gamma action, they found that the iNKT cells could still inhibit Mtb growth in the macrophages.
After testing a few more known mediators of iNKT cell function and finding that they were dispensable as well, the scientists discovered that Mtb control depends on production and release by the iNKT cells of a soluble immune system factor called GM-CSF. When they blocked GM-CSF, they found that iNKT cells could no longer restrict mycobacterial growth. What’s more, when they exposed isolated Mtb-infected macrophages to GM-CSF, they realized this factor alone was sufficient to inhibit Mtb growth.
“Understanding how iNKT cells contribute to the control and elimination of Mtb in general, and finding that GM-CSF has an essential function could lead to novel therapeutic approaches that strengthen their activity and boost the overall immune response during infection,” the study authors note.
