Blood stem cells boost immunity by remembering previous infections

Scientists have discovered that blood stem cells remember previous infections and produce more immune cells, such as macrophages, to fight off a new infection.

A Franco-German research team led by Michael Sieweke, Ph.D., from the Center for Regenerative Therapies TU Dresden (CRTD) and the Center of  Immunology of Marseille Luminy (CNRS, INSERM, Aix-Marseille University) discovered an amazing property of blood stem cells: they not only provide continuous renewal of blood cells and contribute to the immune response caused by foreign agents, but can also remember previous infections in order to stimulate a faster and more effective immune response in the future.

These results will have a significant impact on future vaccination strategies and open the way for new treatments of an underperforming or over-reacting immune system. The results of the study were published in the journal Cell Stem Cell on March 12, 2020.

In the body, stem cells act as reservoirs of cells, which is activated in order to increase its number, as well as differentiate into many different types of specialized cells, necessary to ensure tissue renewal and their functioning.

Usually called blood stem cells, hematopoietic stem cells (HSCs) are located in the bone marrow, which is located inside the cavities of most bones. The role of HSCs is to update various types of blood cells, including cells of the immune system, which are crucial for fighting infections and other diseases.

Ten years ago, it was believed that HSCs are undifferentiated cells that are blind to external signals, such as infections. Only their specialized offspring cells can perceive these signals and activate the immune response. However, the work of the laboratory of Professor Michael Sieweke and other scientists in recent years proved the fallacy of this dogma and showed that HSCs can really perceive external factors in order to produce specific subtypes of immune cells “on demand” to fight an infection.

In addition to their role in the emergency immune response, the question remains of the function of HSCs in responding to repeated episodes of infection. The immune system is known to have a memory that allows it to better respond to the infectious agents that it has encountered before. In this study, scientists tried to establish the leading role of blood stem cells in this kind of memory.

“We discovered that HSCs could drive a more rapid and efficient immune response if they had previously been exposed to LPS, a bacterial molecule that mimics infection”, – said Sandrine Sarrazin, Ph.D., INSERM researcher and senior author of the publication.

Prof. Sieweke, last author of the publication, described how they found the memory was stored within the cells. “The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response”, – he said. “Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come.”

Further, the authors studied how memory was inscribed on the DNA. They showed that the transcription factor C/EBPb is the key factor. This function, unknown until today, is extremely important for emergency immune responses. Together, the findings should help in therapy aimed at improving the tuning of the immune system and improving vaccination strategies.

“The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines. Now that we understand how blood stem cells book mark immune response circuits, we should be able to optimize immunization strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts” – concluded Prof. Sieweke.