Gut Infections Leave ‘Immune Memory’ in the Meninges, Offering Clues to Depression and Anxiety

A study has found that infections or inflammation in the gut leave immune memory in the membranes surrounding the brain, known as the meninges. The finding could offer clues to why gut disorders occur alongside neuropsychiatric symptoms such as depression and anxiety.

According to a study published on the 29th in the international journal Nature Neuroscience, researchers from the University of Cambridge in the United Kingdom and other institutions used experiments in mice to confirm that immune cells activated in the gut migrate to the meninges and remain there long term.

The researchers exposed the mice’s intestines to three stimuli: They fed them a substance that induces colitis, infected them with Salmonella, or exposed them to parasites.

As a result, CD4+ helper T cells activated in the gut left the intestine and migrated to the dura mater, the brain’s outermost membrane. These cells differentiated into different forms depending on the type of threat they encountered. Colitis increased TH17 cells, while Salmonella and parasites increased the proportions of TH1 and TH2 cells, respectively.

The migration was mediated by the CXCR6-CXCL16 signaling pathway. CXCR6 on the surface of T cells draws them to CXCL16 released by dural macrophages, guiding them to their destination. When the researchers blocked this signal, the T cells could not enter dural tissue.

After reaching the dura mater, the T cells settled around venous sinuses, in areas where lymphocytes gather, or inside the brain, forming a population of memory cells that survived for at least 5 months. When the same pathogen invaded again, they mounted an antigen-specific response, rapidly proliferating and releasing defensive substances.

The researchers said, “We experimentally demonstrated that the boundaries of the central nervous system can acquire immune memory against gut microbes,” adding that “the gut is one of the main routes through which pathogens enter the brain via the bloodstream.”

They added, “This pathway could provide new ideas for vaccine design and treatment strategies,” and “could help identify new targets for immune interventions for neurological symptoms associated with enteritis.”