Active Infection & Immunity Brain & Nervous System

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

Funder Wellcome Charity-funded
Recipient organisation University of Manchester
Funding £2.5M
Period Feb 2025 — Jan 2033

In plain English

AI plain-English summary

A chronic brain infection can scramble an animal’s daily activity patterns—and a specific type of immune cell appears to be the reason why. Sleep and circadian rhythms are vital for health, but chronic infections like sleeping sickness disrupt them. The researcher has found that B cells—immune cells normally associated with antibody production—accumulate in brain regions that control sleep during infection with African trypanosomes. In mice engineered to lack these B cells, daily activity cycles become completely abnormal, suggesting the cells actively regulate circadian behaviour and limit brain inflammation. What remains unknown is where these B cells originate and exactly how they influence sleep and activity. This is fundamental science. The work explores a novel connection between the immune system and the brain’s clock during chronic neuroinflammation. If the mechanisms are uncovered, the findings could eventually explain why people with persistent infections—or even long-term inflammatory conditions—often suffer poor sleep. That knowledge might one day inform treatments that protect sleep quality during illness, but the immediate goal is to understand a basic biological interaction that has not been described before.

View original technical description
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.

View the original record at the funder ↗

Researchers

Juan Quintana Alcala (EPMC Awardee)

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Original classification

Career Development Award

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