Our immune system is known to have a memory: once our body has come into contact with a specific pathogen, it can fight back faster and better in the event of a second infection. As researchers now report, surprisingly, the blood stem cells are also involved in this memory function. Accordingly, infections trigger epigenetic changes in the DNA of these cells, which are responsible, among other things, for the production of certain immune cells. As a result, blood stem cells react faster and more efficiently if they become infected again.
The bone marrow is essential for our survival. New blood cells are formed in it every day – for example, red blood cells, but also certain immune system defense cells. This is necessary because many blood cells have a short lifespan and therefore have to be replaced constantly. The so-called hematopoietic stem cells, often simply called blood stem cells, are responsible for this replenishment. Because these cells can differentiate into immune cells, among other things, they play an important role in the fight against infections and other diseases. The blood stem cells are apparently more targeted and efficient than was thought for a long time. Because they can even remember previous infections, as researchers around Bérengère de Laval from the University of Aix Marseille have now found out.
This type of immune memory was previously only known from the already specialized daughter cells of the blood stem cells. The hematopoietic stem cells themselves were, however, “blind” to external signals such as signs of infection. Lately, however, it has already become clear that this assumption is wrong – the stem cells also seemed to be sensitive to external signals. What exactly this means for the reaction to repeated attacks of infection, for example, remained unclear. To change this, the scientists conducted experiments with hematopoietic stem cells in the laboratory. For their study, they exposed blood stem cells to a bacterial molecule called LPS, thereby mimicking an infection. What would happen?
Bookmarks on the DNA
The results showed: Thanks to this previous experience, the blood stem cells reacted differently to a new infection and, among other things, produced more immune cells such as the macrophages known as “phagocytes”. “The blood stem cells can then trigger a faster and more efficient immune response,” reports de Laval’s colleague Sandrine Sarrazin. Accordingly, the stem cells in the bone marrow also have a type of immune memory. In tests, this contributed, among other things, to the defense response of these cells to the bacterium Pseudomonas aeruginosa becoming more effective.
But how does the memory effect come about? Further investigations revealed that the first confrontation with LPS led to epigenetic changes in the blood stem cells: “Marks are deposited on the DNA of the stem cells, precisely around the genes that are important for an immune response,” says co-author Michael Sieweke from the Technical University of Dresden.
As the researcher explains, these markers act like a kind of bookmark: “They make it easier to find these genes and can be activated quickly for an immune response in the event of a second infection by a similar pathogen.” But how do they become “bookmarks “Burned into the genome? De Laval’s team found that a specific protein plays a key role in this. C / EBP regulates gene expression as a transcription factor and apparently also determines where the “bookmarks” are placed on the DNA. “Using this mechanism, the history of infection can be written epigenetically into the hematopoietic stem cells,” the scientists state. The newly discovered process thus represents an essential memory function of the innate immune system.
New approaches for vaccinations and co
The surprisingly good memory of blood stem cells for contagious encounters could lead to new approaches in the future for the treatment of disorders of the immune system and for vaccination strategies. “The ability of our immune system to track previous infections and respond more efficiently the second time is the basic principle of vaccines. With our new understanding of how blood stem cells store information, new immunization strategies are emerging to strengthen protection against infectious agents. Basically, our findings should show new ways of strengthening the immune system if it is too weak or braking if it overreacts, ”concludes Sieweke.
Source: Bérengère de Laval (University of Aix Marseille) et al., Cell Stem Cell, doi: 10.1016 / j.stem.2020.01.017