The human immune system is a bit like a game of Pac-Man: it’s full of cells called macrophages, which hungrily engulf anything they can in order to clear out dead cells and invading “baddies.” However, just as Pac-Man has to eat a Power Pellet in order to be able devour the evil ghosts, so too do these immune cells need to become activated by “eating” a specific type of cell, without which they are unable to respond to tissue damage or bacterial infection. A new study appearing in the journal Cell sheds new light on this process, revealing how macrophages obtain their protective powers.
Unlike the single-minded Pac-Man, macrophages actually perform a range of different tasks, such as monitoring cancerous cells, removing damaged tissue and initiating inflammatory responses to combat infection or injury. The fact that these cells are so versatile raises some intriguing questions regarding how they know which function to perform at which time.
This has led some scientists to speculate that macrophages regularly become “reprogrammed” in order to prime them for the correct course of action. By observing the activity of these cells in fruit flies, the authors of this latest study were able to determine that in order to be able to instigate inflammatory responses, macrophages must first engulf a dead body cell.
“Our study found that immune cells must first become 'activated' by eating a dying neighboring cell before they are able to respond to wounds or infection. In this way, immune cells build a molecular memory of this meal, which shapes their inflammatory behavior,” explained study co-author Helen Weavers.
As fruit fly embryos develop, large numbers of dead cells – called apoptotic cells – are produced and then engulfed by macrophages. When observing the activity of these immune cells, the researchers found that after “eating” this dead material, they expressed greater numbers of a particular type of receptor known as Draper receptors, which play a role in detecting damaged tissue and guiding macrophages to the sites where they are needed.
This, the study authors write, ensures that these cells are primed for inflammatory action precisely when this is required, as explained in the video below.
However, when they genetically engineered fruit fly embryos to lack any apoptotic cells, the researchers discovered that macrophages expressed very low numbers of Draper receptors, and were subsequently unable to respond to tissue damage or bacterial infection.
Observing the mechanism behind this phenomenon, the team discerned that the engulfment of apoptotic cells – via a process called phagocytosis – lead to an influx of calcium across the cell membrane of the macrophage. This, in turn, mobilized an enzyme called JNK, which catalyzed the addition of Draper proteins to the outside of the cell.
To confirm their findings, the researchers then used concentrated blasts of ultraviolet light in order to kill some of the cells in the fruit fly embryos that lacked these, and found that, once these became engulfed by macrophages, an inflammatory response became possible.
According to Weavers, “many human diseases (including atheroscelerosis, cancer and arthritis) are caused or aggravated by an overzealous immune response. A greater understanding of what activates the immune response is therefore crucial for the design of novel therapies to treat these inflammatory disorders.”
For instance, by controlling the activation of macrophages, it may be possible to divert these cells away from the parts of the body where they are doing damage, and towards the areas where they are needed.
Unfortunately, however, this is unlikely to work if your body gets invaded by ghosts.