New map changes understanding of immune cells in the brain

• A major new international study has mapped the immune cells of the brain, known as microglia, in humans and mice. Microglia are thought to play a role in the ongoing damage in progressive MS.
• This map marks a shift in the current understanding of microglia. It shows that there is only a single type of microglia in the brain, but that these cells can change and adapt rapidly.
• The study identified the different characteristics displayed in healthy and diseased brains in mice and humans and showed that the characteristics changed over the course of MS.
• It is hoped that a better understanding of microglia will translate to new treatments that target disability progression in MS.

MS results from immune cells from the blood mistakenly invading the brain and damaging the myelin that coats nerve fibers. In a healthy brain, immune cells generally do not cross from the blood into the brain, but the brain does have its own resident immune cells, known as microglia.

Microglia are thought to play a role in a number of neurological conditions, including MS, Alzheimer’s disease and stroke. As such, the biology of microglia in both health and disease has been of great interest. They are known to perform a supportive role in the brain and can also be helpful after tissue injury, by clearing away debris. However, their activation can also contribute to damage in the brain. This is thought to be part of the process that leads to disability progression in MS.

Previously, there were believed to be a number of different subtypes of microglia, each with a specific job. Now, a new study, published in the prestigious journal Nature, has marked a shift in this understanding and shown that there is only a single type of microglia in the brain, but that they can change their characteristics rapidly to adapt to the situation in which they find themselves.

Using cutting edge technology, the research team, led by Professor Marco Prinz from the University of Freiburg Germany, examined and characterised the cells, one at a time, in mice and human tissue. This technique allowed them to reveal details about the cells that had been undetected in previous analyses, which had only looked at large groups of microglia together.

In mice, they looked at 3,826 individual cells, at different time points in development and at various ages in a healthy brain. They showed that the characteristics of the microglia change over the course of development and in different regions of the brain.

The scientists also looked at different models of disease, including a neurodegenerative disease model and another that mimicked the loss of myelin that is seen in MS. In these two different disease states, the microglia changed in very specific and different ways. The microglia also displayed particular characteristics at different stages of MS, such as when myelin was lost compared to when it was being rebuilt.

The team then went on to look at microglia in human brain tissue. Using the same single cell analysis of 1,180 individual microglial cells, they showed that microglia tended to exist in one of four states in healthy human brain tissue. The researchers then examined 422 individual microglial cells from the brains of five people with confirmed active MS.

They identified that in addition to some of the healthy state microglia, there were also microglia with specific characteristics found in the MS brain which were not present in the healthy brain. Their characteristics suggested these cells play a role in regulating the immune response in the MS brain. Additionally, they looked similar to the microglial states seen in the mouse brain during the stages of myelin loss and myelin rebuilding in MS.

This research is an important step forward in the fundamental understanding of microglia in the brain, and the way that they respond to disease. Due to the intrinsic link between MS progression and the activation of microglia in the brain, it is hoped that a better understanding of the ways microglia function in different stages of MS, in particular during myelin loss and repair, will translate to new treatments that target disability progression in MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.