Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic Trypanosoma brucei infection
Creators
- 1. Wellcome Centre for Integrative Parasitology (WCIP). Institute of Biodiversity, Animal Health, and Comparative Medicine (IBAHCM), MVLS, University of Glasgow, Glasgow UK.
- 2. Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
- 3. Wellcome Centre for Integrative Parasitology (WCIP). MVLS, University of Glasgow, Glasgow UK.
- 4. MRC Centre for Virus Research. University of Glasgow, Glasgow, UK.
- 5. Stanford University School of Medicine, Stanford, CA, United States.
- 6. The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
Description
This repository contains the scripts and processed rds necessary for the analysis of the manuscript titled "Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic Trypanosoma brucei infection"
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 tochronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identified 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 Cx3cr1+ 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.
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Additional details
Related works
- Has part
- Preprint: 10.1101/2022.03.25.485502 (DOI)
Funding
- Molecular basis of parasite-induced disruption of host circadian outputs 221640
- Wellcome Trust
- The skin as a reservoir for trypanosomes: the key to understanding transmission and disease pathology 209511
- Wellcome Trust
- Deciphering developmental commitment in African trypanosomes using single-cell transcriptomics 218648
- Wellcome Trust
References
- Quintana, JQ, et al. (2022). Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic Trypanosoma brucei infection. BioRxiv; DOI: 10.1101/2022.03.25.485502