Gut infections train immune cells to remember—and protect—the brain

Studies in mice show that immune cells that fight intestinal worms can migrate from the gut to the brain, where they establish a lasting “memory” of previous infections.

The brain is protected by membranes called the meninges, which shield the central nervous system from pathogens circulating in the blood. When mice were infected with bacteria and parasites that cause intestinal disease, immune cells migrated from the intestines to the meninges. Once there, the cells became resident immune cells and responded to a second infection more than a month after the first, suggesting that they retained a record of the earlier illness.

Francisco Quintana, a neuroimmunologist at Harvard University in Cambridge, Massachusetts, described the study as “outstanding”. He said it could help researchers understand how the gut interacts with the central nervous system.

“This opens up several possibilities, including investigating how intestinal infections affect neurological diseases and developing treatments that exploit that relationship,” he says.

The results were published last week in Nature Neuroscience.¹

Immune cells on the move

Previous research has shown that, under healthy conditions, certain types of immune cells found in the intestines are also present in the meninges. But few studies have investigated whether the intestine and meninges share immune cells that respond to gastrointestinal infections, says study co-author Menna Clatworthy, a clinical scientist at the University of Cambridge, UK.

To investigate, Clatworthy and her colleagues infected mice with pathogens that cause intestinal disease, including food-poisoning bacteria. These included Citrobacter rodentium and Schistosoma mansoni, a parasite that causes a tropical disease known as snail fever.

The researchers then examined CD4⁺ T cells, which help direct other immune cells to fight infections, in the intestines and meninges.

Before infection, CD4⁺ T cells made up only a small proportion of the immune cells found in the meninges. Three weeks after the mice were infected with C. rodentium, the number of T cells expressing the protein IL-17 surged in both the intestines and meninges. These T cells are known to target C. rodentium.

Six weeks after infection with S. mansoni, the number of T cells directed against the parasite had increased in both tissues.

Clatworthy and her colleagues sequenced tissue from the intestine and meninges and found identical T-cell receptors in both locations. This indicated that T cells trained in the intestine had migrated to the meninges after infection. The researchers also discovered that the cells rely on signaling molecules called chemokines to travel through the bloodstream to the meninges.