Immune cells of the blood might replace dysfunctional brain cells

Blood-circulating immune cells can take over the essential immune surveillance of the brain, this is shown by scientists of the German Center for Neurodegenerative Diseases and the Hertie Institute for Clinical Brain Research in Tübingen. Their study, now published in PNAS, might indicate new ways of dealing with diseases of the nervous system.

The immune system is comprised of multiple cell types each capable of specialized functions to protect the body from invading pathogens and promote tissue repair after injury. One cell type, known as monocytes, circulates throughout the organism in the blood and enters tissues to actively phagocytose (eat!) foreign cells and assist in tissue healing. While monocytes can freely enter most bodily tissues, the healthy, normal brain is different as it is sequestered from circulating blood by a tight network of cells known as the . Thus, the brain must maintain a highly specialized, resident immune cell, known as , to remove harmful invaders and respond to tissue damage.

In certain situations, such as during disease, monocytes can enter the brain and also contribute to tissue repair or disease progression. However, the potential for monocytes to actively replace old or injured microglia is under considerable debate. To address this, Nicholas Varvel, Stefan Grathwohl and colleagues from the German Center for (DZNE) Tübingen and the Hertie Institute for Clinical in Tübingen used a in which almost all brain microglia cells (>95%) can be removed within two weeks. This was done by introducing a so-called into microglia cells and administering a pharmaceutical agent that leads to acute death of the cells. Surprisingly, after the ablation of the microglia, the brain was rapidly repopulated by blood-circulating monocytes. The monocytes appeared similar, but not identical to resident microglia. The newly populated monocytes, evenly dispersed throughout the brain, responded to acute neuronal injury and other stimuli—all activities normally assumed by microglia. Most interestingly, the monocytes were still present in the brain six months - nearly a quarter of the life of a laboratory mouse - after initial colonization.

These studies now published in PNAS provide evidence that blood-circulating monocytes can replace brain resident microglia and take over the essential of the brain. Furthermore, the findings highlight a strong homeostatic mechanism to maintain a resident immune cell within the brain. The observation that the monocytes took up long-term residence in the brain raises the possibility that these cells can be utilized to deliver therapeutic agents into the diseased brain or replace microglia when they become dysfunctional. Can monocytes be exploited to combat the consequences of Alzheimer's disease and other neurodegenerative diseases? The scientists and their colleagues in the research groups headed by Mathias Jucker are now following exactly this research avenue.

More information: "Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells", Nicholas H. Varvel, Stefan A. Grathwohl, Frank Baumann, Christian Liebig, Andrea Bosch, Bianca Brawek, Dietmar R. Thald, Israel F. Charo, Frank L. Heppnerf, Adriano Aguzzi, Olga Garaschuk, Richard M. Ransohoff, and Mathias Jucker, Proceedings of the National Academy of Sciences (PNAS): www.pnas.org/cgi/doi/10.1073/pnas.1210150109

Related Stories

Scientists discover origin of brain immune cells

Oct 27, 2010

A team of international scientists led by Dr Florent Ginhoux of the Singapore Immunology Network (SIgN) of Singapore's Agency of Science, Technology and Research (A*STAR), have made a breakthrough that could lead to a better ...

Researchers discover origin of immune cells in the brain

Oct 22, 2010

Mount Sinai researchers have discovered that microglia, the immune cells that reside in the brain, have a unique origin and are formed shortly after conception. It was previously thought that microglia originated at the ...

Key signal prepares immune cells to defend skin, brain

Aug 10, 2012

(Medical Xpress) -- Scientists at Washington University School of Medicine in St. Louis have identified the molecular signal that triggers the development of immune cells that patrol the skin and brain.

Recommended for you

Team reprograms blood cells into blood stem cells in mice

9 hours ago

Researchers at Boston Children's Hospital have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs), using a cocktail of eight genetic switches called transcription factors. The reprogrammed ...

User comments