Authors

J Quintana¹;  ¹ University of Manchester, UK

Discussion

One fascinating aspect of Human African Trypanosomiasis, also known as sleeping sickness, is the profound effects this infection has on the brain, which in turn affects a wide range of behaviours, from feeding to sleep. However, the basis of such behavioural disturbances is far from being fully understood. This could in turn teach us how the brain operates under stressful conditions such as inflammation. In this talk, I will cover the work my team and I have conducted to address this gap in knowledge from an immunological point of view. In a nutshell, I discovered that brain-resident B cells play opposing roles locally during infection, from limiting brain inflammation via anti-inflammatory cytokines (Quintana et al, Nat comms, 2022) to inducing autoimmunity (Quintana et al. PLoS Biology, 2023), indicating that sleeping sickness is much more complex than previously anticipated. Serendipitously, my preliminary studies show that mice devoid of a particular type of B cells, known as regulatory B cells, show more severe neuroinflammation and are unable to sustain normal behaviour under homeostasis and during infection compared to littermate controls, highlighting the importance of these cells in supporting brain homeostasis and resilience. Together, these observations indicate that brain-derived B cells are not only functionally heterogeneous (e.g., regulatory vs. pathological) but essential to control how the brain works. Moving forward, my laboratory will investigate the origin and functional diversity of B cells in the brain, how these cells control the immunological landscape in this organ during infection, and the consequences of such neuroimmune interactions for behaviour, placing brain-resident B cells as guardians of the brain’s integrity and function.
Selected publications: 1. Quintana JF, et al. Single cell and spatial transcriptomics analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection. Nat commun, 13, 5752 (2022). 2. Quintana JF, et al. The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection. PLoS Biol, 21(11): e3002389 (2023).