Filming how our immune system kills bacteria

To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets. UCL scientists have filmed these nanomachines in action, uncovering a bottleneck in the process that helps protect our own cells.

The research, published in Nature Communications, allows us to better understand how the immune system kills bacteria and why our own cells remain intact. This could guide the development of new treatments that exploit the immune system against bacterial infections and strategies that reorient the immune system against other dishonest cells in the body.

In previous research, scientists analyzed the characteristics of the attack in live bacteria, showing that the immune system's response resulted in "bullet holes" distributed in the cell envelopes of the bacteria. The holes are incredibly small with a diameter of only 10 nanometers.

For this study, the researchers imitated how these deadly holes are formed by the membrane attack complex (MAC) using a model bacterial surface. By following each step of the process, they found that shortly after the start of each hole formation, the process was blocked, providing a recovery for the body's own cells.

"It seems like these nanomachines are waiting a moment, allowing their potential victim to intervene in case he 's acting from a cell of the body instead of an invasive insect, before it' s. They do not carry the fatal blow, "said Dr. Edward Parsons (UCL London Center). for nanotechnology).

The team said the process was suspended, with 18 copies of the same protein needed to complete a hole. Initially, only one copy is inserted into the bacterial surface, after which the other copies of the protein slice are put in place much more quickly.

"It is the insertion of the first protein of the membrane attack complex that causes the bottleneck in the process of destruction. Oddly enough, it coincides with the point where the formation of holes is prevented on our own healthy cells, leaving them intact, "said Professor Bart. Hoogenboom (UCL Physics & Astronomy).

To film the immune system in action at a nanoscale resolution and seconds per image, scientists used atomic force microscopy. This type of microscopy uses an ultrafine needle to feel rather than see molecules on a surface, similar to a blind person who reads Braille. The needle sweeps the surface repeatedly to produce an image that refreshes itself quickly enough to track how the immune proteins assemble and lodge in the bacterial surface.