Our immune system relies heavily on nanomachines that can open deadly holes in their targets to kill the bacteria in our blood. Scientists from UCL have filmed the nanomachine in action to discover a key bottleneck process that can help protect our cells.
The research was published in Nature Communications, and it provides us with a better and deeper understanding of how our immune system kills the bacteria and why our cells remain intact after. This could help guide the development of new therapies that can harness our immune system against bacterial infections and different strategies that can repurpose our immune system so they can act against rogue cells in our body.
In earlier studies, scientists had imaged the hallmarks of attack in live bacteria. It shows that our immune system response in a way that results to "bullet holes" that spread across the cell envelope of the bacteria. The "bullet holes" are so small, it has a diameter of 10 nanometers.
For this new study, the researchers now mimicked how the holes are formed by the MAC or the membrane attack complex using a model bacterial surface. By tracking the step of the process, they found that immediately after the hole started to form, the whole process stalled, and it offered a reprieve for the cells.
"It appears as if these nanomachines wait a moment, allowing their potential victim to intervene in case it is one of the body's own cells instead of an invading bug, before they deal the killer blow," explained Dr. Edward Parsons from the UCL London Centre for Nanotechnology.
The scientists say that the process pauses because 18 copies of the same protein are needed in order to complete a hole. There was only one copy which inserts into the bacterial surface, and right after the other copies of the protein gets into place much faster.
"It is the insertion of the first protein of the membrane attack complex which causes the bottleneck in the killing process. Curiously, it coincides with the point where hole formation is prevented on our own healthy cells, thus leaving them undamaged," said Professor Bart Hoogenboom from UCL Physics & Astronomy.
In order to film the immune system in action, the scientists used atomic force microscopy so they can film it at nanometer resolution and a few seconds per frame. This kind of microscopy uses an ultrafine needle to feel molecules on a surface instead of seeing them, it is similar to a visually impaired person reading Braille. The needle scans the surface repeatedly to produce an image that refreshes fast so it can track how the immune proteins get together and how the cut into the bacterial surface.
