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

التفاصيل البيبلوغرافية
العنوان: Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection.
المؤلفون: Quintana JF; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK. juan.quintana@glasgow.ac.uk.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK. juan.quintana@glasgow.ac.uk., Chandrasegaran P; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK., Sinton MC; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK., Briggs EM; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK., Otto TD; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Infection and Immunity, MVLS, University of Glasgow, Glasgow, UK., Heslop R; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK., Bentley-Abbot C; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK., Loney C; School of Infection and Immunity, MVLS, University of Glasgow, Glasgow, UK.; MRC Centre for Virus Research, University of Glasgow, Glasgow, UK., de Lecea L; Stanford University School of Medicine, Stanford, CA, USA., Mabbott NA; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK., MacLeod A; Wellcome Centre for Integrative Parasitology (WCIP), University of Glasgow, Glasgow, UK.; School of Biodiversity, One Health, and Veterinary Medicine (SBOHVM), MVLS, University of Glasgow, Glasgow, UK.
المصدر: Nature communications [Nat Commun] 2022 Sep 30; Vol. 13 (1), pp. 5752. Date of Electronic Publication: 2022 Sep 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Parasites* , Trypanosoma brucei brucei*/genetics , Trypanosomiasis, African*/parasitology, Animals ; B-Cell Activating Factor ; Brain/parasitology ; Humans ; Interleukin-10 ; Mice ; Microglia ; Plasma Cells ; Transcriptome
مستخلص: 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.
(© 2022. The Author(s).)
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معلومات مُعتمدة: 218648/Z/19/Z United Kingdom WT_ Wellcome Trust; BBS/E/D/20002174 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 221640/Z/20/Z United Kingdom WT_ Wellcome Trust; 204820/Z/16/Z United Kingdom WT_ Wellcome Trust; 104111/Z/14/ZR United Kingdom WT_ Wellcome Trust; BBS/E/D/20231762 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; United Kingdom WT_ Wellcome Trust; 209511/Z/17/Z United Kingdom WT_ Wellcome Trust; MC_UU_12014/7 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (B-Cell Activating Factor)
130068-27-8 (Interleukin-10)
تواريخ الأحداث: Date Created: 20220930 Date Completed: 20221004 Latest Revision: 20231102
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9525673
DOI: 10.1038/s41467-022-33542-z
PMID: 36180478
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-022-33542-z