Mast Cells’ Role in Defending the Brain Revealed in New Study

While mast cells are well known for causing the itching, redness, and swelling associated with allergic reactions, new research from Washington University School of Medicine in St. Louis has revealed a different and crucial role for these immune cells. The study, published in Cell, demonstrates that mast cells help protect the brain from bacterial and viral infections in mice by acting as guardians at tiny entry points where fluid waste leaves the brain.

These small gates are located in the meninges, the tissue layers that surround the brain beneath the skull. Normally, these openings permit the flow of brain fluid out into lymphatic vessels, where immune cells monitor for potential threats. However, these same pathways could become entry routes for bacteria or viruses to access the brain. Senior author Jonathan Kipnis explains, “We now know how mast cells shield the brain, so we can explore enhancing their function during the threat of infections.” The researchers point out that their findings could lead to new ways of preventing or treating serious brain infections such as bacterial meningitis. 

The team, including first author Tornike Mamuladze, studied mice infected with either Streptococcus agalactiae or S. pneumoniae, both causes of meningitis. They observed that infected mice had reduced brain fluid flow through the gates compared to healthy ones. The presence of bacteria triggered mast cells in the meningeal tissues to release granules containing histamine, causing nearby veins to dilate. This dilation temporarily closed the path through which brain fluid—and potentially bacteria—would pass, thereby creating a barrier to infection.

Their experiments further revealed that activated mast cells summon other immune cells, such as neutrophils, to the area to help destroy bacteria. Mice lacking mast cells were more likely to have bacteria infiltrate the brain, while boosting mast cell activity prior to infection lowered the bacterial load. 

Kipnis cautions, though, that long-term mast cell activation could have downsides, as it blocks fluid movement and might cause waste like amyloid beta to accumulate in the brain. The research group aims to explore whether chronic activation of mast cells could negatively impact conditions such as Alzheimer’s disease. As first author Mamuladze points out, understanding how to regulate mast cells at these brain gateways is critical for protecting against infection while maintaining healthy brain function.