Browse by author
Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 3(rd) 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.
Author(s): Quintana JF, Chandrasegaran P, Sinton MC, Briggs EM, Otto TD, Heslop R, Bentley-Abbot C, Loney C, de Lecea L, Mabbott NA, MacLeod A
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2022
Volume: 13
Issue: 1
Print publication date: 30/09/2022
Online publication date: 30/09/2022
Acceptance date: 21/09/2022
Date deposited: 29/01/2025
ISSN (print): 0028-0836
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41467-022-33542-z
DOI: 10.1038/s41467-022-33542-z
Data Access Statement: The data generated in this study have been deposited in the Gene Expression Omnibus database under accession code GSE200642. The processed transcript count data and cell metadata generated in this study are available at Zenodo (https://zenodo.org/record/ 6387555#.YwkaFi8w1nk)103 . The flow cytometry data generated in this study are provided in the Supplementary Information/Source Data file. Additional data and files can also be sourced via Supple- mentary Datas. Source data are provided with this paper. The single cell dataset can be explored in this link: https://cellatlas-cxg.mvls.gla. ac.uk/tbrucei_brain/. Source data are provided with this paper.
PubMed id: 36180478
Altmetrics provided by Altmetric
