The brain’s inner workings have traditionally been viewed as separate from “unconscious” physiological functions like immunity. Yet, recent research has uncovered a surprising degree of reciprocal brain-immune system interaction. For example, biomarkers of peripheral immunity influence brain aging and cognition, and dopamine-rich reward circuits in the brain influence systemic antibacterial activity in immune cells. A recent study now reveals that specific brain cells store memories of the body’s past experiences with infections, potentially reawakening previous immune responses.

The researchers first measured brain activity in a group of mice that had inflammatory bowel disease. Their measurements revealed that the bowel inflammation and its associated immune response generated a broad pattern of activity across several regions of the brain, especially the insular cortex, a region considered crucial for receiving and processing information about internal bodily states and immune system activities.

Then, to test whether the pattern of neuronal activity in the insular cortex represented a true memory of bowel inflammation, they examined how the mice reacted when the insular neurons were reactivated four weeks after the animals' recovery from illness. The result was a near-perfect revival of the original immune response to bowel inflammation, including a surge of white blood cells to the colon, heightened activation of a range of T-cells specialized for sensing and attacking pathogens, and a spike in pro-inflammatory molecules such as interleukins and tumor necrosis factor-alpha.

The brain-induced immune event exhibited two features that indicated it was a form of recollection. First, it was exclusively located in the colon, suggesting a relatively precise “memory” of bowel inflammation rather than a generic signal for immune defense. Second, a repeated experience with simulated bowel disease caused the insular cortex to generate a new and largely non-overlapping pattern of immune-triggering activity. This indicates that the insular cortex is capable of “remembering” distinct episodes of the body’s encounters with disease.

This study provides some of the first causal evidence that brain cells can form memories of past immune reactions – a property that may have evolved to help bodily tissues become faster and more precise in how they tackle future infections. While the mechanisms of these neuro-immune interactions are not fully understood, the interactions offer the potential for targeted insular brain stimulation to treat severe autoimmune and inflammatory health conditions.

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