How the Gut Protects the Brain Against Infections

The brain is the most important organ in our body. It is the control tower that sends information all over the body, the seat of our intelligence and our emotions. To protect itself from external dangers, it is assisted by our skull, an extremely strong set of bones. On the other hand, to defend itself against infections, it calls upon… our intestine. This was discovered by researchers from the University of Cambridge (United Kingdom) and the National Institute of Health (United States). They published their results on November 4, 2020 in the journal Nature.

Until now, the scientific community did not fully understand the brain’s defense mechanism against viruses and bacteria. Unlike other organs, which are also irrigated by blood and which can be infected by parasites, the brain seemed relatively spared. For all the other organs, it is the antibodies and the white blood cells of the immune system that ensure their protection, but this is impossible for the brain, because of the meninges which form an impermeable barrier to these cells, which is called the blood-brain barrier.

Brain irrigation pathways under surveillance

To better understand how this protection occurs, the researchers studied mice, which share characteristics similar to those of the human body. They realized that the meninges of these rodents house plasma cells, a type of B lymphocyte. Normally, plasma cells are not found in the blood or in the lymph. Similarly, plasma cells give rise to antibodies to provide protection to the body.

In mice, plasma cells are located at the edge of blood vessels that pass through the meninges, allowing them to secrete antibodies to defend the perimeter around the brain. On closer inspection, the antibodies present in the meninges are immunoglobulins A (IgA), while those which must come into contact with the blood are immunoglobulins B (IgB). Normally, IgA is found in the mucous membranes, whether in the nose or lungs, but mainly in the intestinal mucosa.

When sequencing the antibody genes, the teams found that plasma cells in the meninges and intestine were linked. To put it simply, the cells found in the meninges are the same as those which develop in the intestine, and which respond to the same rules of defense against pathogenic agents.

Gut antibodies to protect the brain

“Exactly how the brain protects itself from infection, beyond the physical barrier of the meninges, is somewhat of a mystery, but discovering that an important line of defense begins in the gut was a surprise., but when you think about it, it makes perfect sense, underlines Menna Clatworthy, professor in the department of medicine at the University of Cambridge. Even a small breach in the intestinal barrier will allow bacteria to enter the bloodstream, with devastating consequences if they are able to spread to the brain. Seeding the meninges with antibody-producing cells selected to recognize gut microbes provides defense against the most likely invaders.”

Researchers realized the importance of the gut by observing mice; when they have no bacteria in the intestine, the cells produced by the plasma cells of the meninges are IgA. Once the intestine is infected with parasites, they find IgB near the meninges. By removing the plasma cells from the meninges – and therefore by removing the immunoglobulins responsible for trapping the parasites – the microbes were able to spread from the bloodstream to the brain.

The team confirmed the presence of immunoglobulin A in human meninges by analyzing samples, which shows that this defense system plays an important role in protecting the central nervous system — meninges and brain — against parasites.