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Gut bacteria instruct brain cells to fight inflammation

  • Star-shaped brain cells called “astrocytes” are key in regulating the development of other nerve cells.
  • However, malfunctioning astrocytes can play roles in inflammation and the deterioration of nerve cells.
  • A new study in mice has identified a previously undescribed type of astrocyte, which, the researchers say, may actually protect against inflammation.
  • The study has also revealed that the newly identified astrocyte type receives signals from gut bacteria, which appear to boost its anti-inflammatory activity.

A newly discovered type of brain cell combats inflammation when it receives signals from bacteria in the gut. This finding — of research in animals — might lead to the development of probiotics that help reduce inflammation in people with neurological disorders such as multiple sclerosis (MS).

Star-shaped brain cells called astrocytes perform a wide range of maintenance services in the brain. These include providing nutrients to nerve cells and regulating the cells’ development.

When astrocytes malfunction, however, they can promote inflammation and neurodegeneration.

Research suggests that faulty astrocytes are involved in a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases.

Now, a new study in mice has found that a previously unknown type of astrocyte actually protects against inflammation. More surprisingly, the cell steps up its anti-inflammatory work when it receives a molecular signal from gut bacteria.

“Over the years, many labs, including mine, have identified important roles for astrocytes in promoting neurological diseases,” says Dr. Francisco Quintana, of the Ann Romney Center for Neurologic Diseases, at Brigham and Women’s Hospital, in Boston, MA. Dr. Quintana is the senior and corresponding author of the new study.

He says this is the first known instance of astrocytes preventing inflammation.

“The reason we haven’t seen this before was because we were studying these cells as if they were uniform, or one single cell type,” Dr. Quintana explains. “But now we have the resolution to see the differences between these cells.”

The results of the study have been published in Nature.

Anti-inflammatory astrocytes

The scientists discovered the new type of astrocyte using molecular tools for determining the activity of genes and the proteins they produce, or “express.”

Uniquely, the astrocytes in question express two proteins, called LAMP1 and TRAIL. So the researchers call them LAMP1+TRAIL+ astrocytes. They are found close to the meninges, the protective membranes that envelop the brain and spinal cord.

This type of astrocyte appears to limit inflammation in the brain by expressing the TRAIL protein, say the researchers. When TRAIL binds to death receptors in the membranes of immune cells that promote inflammation, this induces the cells to self-destruct.

Further investigations revealed that an immune signaling molecule called interferon gamma induces LAMP1+TRAIL+ astrocytes to produce TRAIL and hence control inflammation.

Immune cells known as natural killer cells, which can destroy cancerous cells and those infected with viruses, generate interferon gamma. Following the trail back still further, the scientists found that the gut microbiome induces natural killer cells to produce interferon gamma.

The activated cells find their way via the bloodstream to the meninges, where they help reduce inflammation.

Gut microbiome

It is becoming clear that the community of microorganisms that inhabit our gut, known as the gut microbiome, plays a prominent role in many diseases.

In previous research, Dr. Quintana’s lab identified the only other type of astrocyte known to be regulated by the gut microbiome, but there are almost certainly others.

“We’re lucky that we’ve been leading the charge to identify different subsets of astrocytes and the mechanisms that control them. We have a list of other populations of astrocytes, and we’re working to see how the gut flora may control them.”

– Dr. Francisco Quintana

Understanding what drives the anti-inflammatory ability of LAMP1+TRAIL+ astrocytes could enable medical researchers to develop new treatments for neurological diseases, such as MS, in which inflammation plays a part.

The team is already investigating probiotic species that could regulate the anti-inflammatory activities of astrocytes.

Inflammation is a crucial tool in the body’s immune response to infections and tumor cells. It only becomes a problem when it goes out of control.

Recent work by Dr. Quintana and colleagues suggests that certain brain tumors can exploit the pathway they identified in the current study to evade the brain’s inflammatory defenses.

So the scientists are also looking at ways to block this strategy, making cancerous cells vulnerable to inflammation once again.

It should be emphasized that their work on astrocytes and inflammation remains at an early stage, focusing on animal models of human disease.

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  • Posted on January 29, 2021