Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

Juan F. Quintana (), Praveena Chandrasegaran, Matthew C. Sinton, Emma M. Briggs, Thomas D. Otto, Rhiannon Heslop, Calum Bentley-Abbot, Colin Loney, Luis de Lecea, Neil A. Mabbott and Annette MacLeod
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Juan F. Quintana: University of Glasgow
Praveena Chandrasegaran: University of Glasgow
Matthew C. Sinton: University of Glasgow
Emma M. Briggs: University of Glasgow
Thomas D. Otto: University of Glasgow
Rhiannon Heslop: University of Glasgow
Calum Bentley-Abbot: University of Glasgow
Colin Loney: University of Glasgow
Luis de Lecea: Stanford University School of Medicine
Neil A. Mabbott: University of Edinburgh
Annette MacLeod: University of Glasgow

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and induces profound reactivity of glial cells and neuroinflammation when the parasites colonise the central nervous system. However, the transcriptional and functional responses of the brain to chronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identify that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle. This coincides with the spatial localisation of both slender and stumpy forms of T. brucei. Furthermore, in silico predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic microglia and Cd138+ plasma cells mediated by IL-10 and B cell activating factor (BAFF) signalling. This study provides important insights and resources to improve understanding of the molecular and cellular responses in the brain during infection with African trypanosomes.

Date: 2022
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DOI: 10.1038/s41467-022-33542-z

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