Mapping the brain's immune system

German researchers have created an entirely new map of the brain’s own immune system in humans and mice, demonstrating in the process that the phagocytes in the brain — the so-called microglia — all have the same core signature but adapt in different ways depending on their function.

Since the immune cells located in the blood cannot reach the brain and spinal cord on account of the blood–brain barrier, the brain needs its own immune defence: the microglia. These phagocytes of the brain develop very early on in the process of embryonic development and later remove invading germs and dead nerve cells. They also contribute to the maturation and lifelong malleability of the brain.

It was previously unclear whether there are subtypes of microglia for the various functions they serve in the healthy and diseased brain. Seeking an answer, a research team led by the Medical Center – University of Freiburg conducted detailed studies on microglia in the brain, both on a mouse model and on human brain tissue removed from patients.

With the help of a new, high-resolution method for conducting single-cell analysis, the researchers were able to demonstrate the features of microglia in great detail. To do so, they used a microscope to study microglia in different brain regions and at different stages of development. They also analysed the RNA levels of these cells using single-cell analysis.

Analysis revealed that microglia all have the same core signatures but adapt differently at different stages of development, in different brain regions and depending on the function they are meant to serve. The study results were published in the journal Nature.

“We were able to show that there is only a single type of microglia in the brain that exists in multiple flavours,” said project head Professor Dr Marco Prinz, Medical Director of the Institute of Neuropathology at the Medical Center – University of Freiburg. “These immune cells are very versatile all-rounders, not specialists, as has been the textbook opinion up to now.”

Single-cell analysis of microglia. Each point shows a cell, and the colour signals how strongly particular immunologically significant genes are activated in the various cells. Image credit: Takahiro Masuda/Medical Center – University of Freiburg.

The discovery is important for our understanding of brain diseases, with dysregulated microglia playing a key role in the development of Alzheimer’s, multiple sclerosis (MS) and psychiatric diseases like autism. In healthy brains, microglia form a uniform network around the nerve cells that can change in just a few minutes in the case of disease and form numerous new phagocytes to limit the damage.

“We now possess the first high-resolution immune cell atlas of the human brain. This also enables us to understand how these cells change during course of diseases like MS,” Prof Prinz said. “In MS patients, we managed to characterise microglia in a state that is specific for multiple sclerosis. We hope that it will be possible in the future to target microglia subsets in harmful state.

“It is extremely exciting to see how flexible the microglia can be.”

Top image credit: ©stock.adobe.com/au/vege

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