Gut Trains Immune System to Protect Brain
The membranes surrounding our brains are in a never-ending battle against deadly infections, as germs constantly try to elude watchful immune cells and sneak past a special protective barrier called the meninges. In a study involving mice and human autopsy tissue, researchers at NIH and Cambridge University have shown that some of these immune cells are trained to fight these infections by first spending time in the gut.
“This finding opens a new area of neuroimmunology, showing that gut-educated antibody-producing cells inhabit and defend regions that surround the central nervous system,” said Dr. Dorian McGavern, senior investigator at NINDS and co-senior author of the study, which was published in Nature.
The central nervous system (CNS) is protected from pathogens both by a three-membrane barrier called the meninges and by immune cells within those membranes. The CNS is also walled off from the rest of the body by specialized blood vessels that are tightly sealed by the blood-brain barrier. This is not the case, however, in the dura mater, the outermost layer of the meninges. Blood vessels in this compartment are not sealed, and large venous structures, referred to as the sinuses, carry slow-moving blood back to the heart. The combination of slow blood flow and proximity to the brain requires strong immune protection to stop potential infections in their tracks.
“The immune system has invested heavily in the dura mater,” said McGavern. “The venous sinuses within the dura act like drainage bins, and, consequently, are a place where pathogens can accumulate and potentially enter the brain. It makes sense that the immune system would set up camp in this vulnerable area.”
In this study, McGavern’s team worked with researchers in a lab led by Dr. Menna Clatworthy of the UK’s University of Cambridge to look at what immune cell types reside in the outer layers of the meninges of mice and humans. What they discovered was rather surprising: there were many immune cells previously educated to make antibodies against specific microbes. These antibody-producing cells, called IgA cells, are typically found in other barriers such as the mucous membranes of the bronchial tree of the lungs and gut.