Gut-trained immune cells migrate directly from the digestive tract into the brain's protective membranes and establish a lasting record of previous infections, according to a mouse study reported by Nature.
Menna Clatworthy, a clinician scientist at the University of Cambridge, investigated how the gut and the central nervous system exchange defensive cells during active sickness. Protective membranes known as meninges shield the brain from pathogens circulating in the bloodstream. While previous research confirmed that healthy meninges house certain immune cells also found in the gut, few studies had examined whether the two sites share cells responding to gastrointestinal infections.
The authors exposed mice to common intestinal threats, including the food-poisoning bacterium Citrobacter rodentium and Schistosoma mansoni, a parasitic worm responsible for snail fever. The team then tracked CD4+ T cells, which guide other immune cells during an immune response. Prior to infection, CD4+ T cells accounted for only a minor fraction of the immune population in the meninges. Three weeks after bacterial infection, T cells expressing the IL-17 protein spiked simultaneously in the gut and meninges. Six weeks following parasitic infection, worm-fighting T cells increased across both tissues.
Clatworthy's team sequenced tissue from both sites and identified identical T-cell receptors in each organ. That match proved that gut-primed T cells travelled to the meninges through the bloodstream, relying on chemical signalling molecules called chemokines to navigate the journey.
These relocated cells remained in the meninges and mounted a defence against a second infection more than a month later. Francisco Quintana, a neuroimmunologist at Harvard University, said the findings were outstanding and could help researchers examine how intestinal infections influence neurological disorders and develop therapies targeting the relationship.
