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

Juan F. Quintana; Praveena  Chandrasegaran; Matthew C.  Sinton; Emma Marie Briggs; Thomas Dan Otto; Rhiannon  Heslop; Calum  Bentley-Abbot; Colin Loney; Luis  de Lecea; Neil Mabbott; Annette MacLeod

doi:10.1038/s41467-022-33542-z

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

Juan F. Quintana^*, Praveena Chandrasegaran, Matthew C. Sinton, Emma Marie Briggs, Thomas Dan Otto, Rhiannon Heslop, Calum Bentley-Abbot, Colin Loney, Luis de Lecea, Neil Mabbott, Annette MacLeod

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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+ 51 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.

Original language	English
Article number	5752
Journal	Nature Communications
Volume	13
Issue number	1
Early online date	30 Sept 2022
DOIs	https://doi.org/10.1038/s41467-022-33542-z
Publication status	Published - 30 Sept 2022

Access to Document

10.1038/s41467-022-33542-z

Quintana-NatComms-accepted-092122 (1)Accepted author manuscript, 1.6 MBLicence: Creative Commons: Attribution (CC-BY)
s41467-022-33542-zFinal published version, 11.4 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

Quintana, J. F., Chandrasegaran, P., Sinton, M. C., Briggs, E. M., Otto, T. D., Heslop, R., Bentley-Abbot, C., Loney, C., de Lecea, L., Mabbott, N., & MacLeod, A. (2022). Single cell and spatial transcriptomic reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection. Nature Communications, 13(1), Article 5752. https://doi.org/10.1038/s41467-022-33542-z

@article{f4e225796ed3412cbaad8d508d012608,

title = "Single cell and spatial transcriptomic reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection",

abstract = "Human African trypanosomiasis, or sleeping sickness, is caused by the protozoanparasite Trypanosoma brucei and induces profound reactivity of glial cells andneuroinflammation 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+ 51 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 = "Quintana, {Juan F.} and Praveena Chandrasegaran and Sinton, {Matthew C.} and Briggs, {Emma Marie} and Otto, {Thomas Dan} and Rhiannon Heslop and Calum Bentley-Abbot and Colin Loney and {de Lecea}, Luis and Neil Mabbott and Annette MacLeod",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = sep,

day = "30",

doi = "10.1038/s41467-022-33542-z",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Single cell and spatial transcriptomic reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

AU - Quintana, Juan F.

AU - Chandrasegaran, Praveena

AU - Sinton, Matthew C.

AU - Briggs, Emma Marie

AU - Otto, Thomas Dan

AU - Heslop, Rhiannon

AU - Bentley-Abbot, Calum

AU - Loney, Colin

AU - de Lecea, Luis

AU - Mabbott, Neil

AU - MacLeod, Annette

PY - 2022/9/30

Y1 - 2022/9/30

N2 - Human African trypanosomiasis, or sleeping sickness, is caused by the protozoanparasite Trypanosoma brucei and induces profound reactivity of glial cells andneuroinflammation 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+ 51 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.

AB - Human African trypanosomiasis, or sleeping sickness, is caused by the protozoanparasite Trypanosoma brucei and induces profound reactivity of glial cells andneuroinflammation 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+ 51 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.

U2 - 10.1038/s41467-022-33542-z

DO - 10.1038/s41467-022-33542-z

M3 - Article

C2 - 36180478

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5752

ER -

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

Abstract / Description of output

Access to Document

Fingerprint

Cite this