How do CNS border-derived B-cells shape brain immunity and behaviour during chronic infections?

Circadian rhythms and sleep are extremely important processes impacting both our physical and mental health. However, when we experience chronic infections, such as Human African trypanosomiasis or sleeping sickness, our circadian and sleep patterns are disrupted, potentially affecting the quality of the immune response necessary to fight infections. Using African trypanosomes as a model infection, I recently identified that a specialised group of immune cells, known as B cells, accumulate in brain areas controlling sleep in response to infection, and produce molecules that limit brain inflammation. Using genetically engineered mice deficient for these B cells, I observed that these animals show completely aberrant daily activity patterns, suggesting that B cells are necessary to control circadian behaviour and sleep. However, it is unclear where these B cells come from during infection, or how they control circadian activity and sleep. Throughout this award, I will explore the exciting and novel interactions between the immune system, the brain, and sleep and circadian behaviour during chronic infection-induced neuroinflammation. This knowledge can be applied to understand why the quality of our sleep is poor during infections, and the downstream consequences such disruptions have on immunity.