{"doi":"10.1101/2022.03.25.485502","title":"Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic\n                  <i>Trypanosoma brucei</i>\n                  infection","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite\n                  <jats:italic>Trypanosoma brucei</jats:italic>\n                  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\n                  <jats:italic>T. brucei</jats:italic>\n                  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 3\n                  <jats:sup>rd</jats:sup>\n                  ventricle. This coincides with the spatial localisation of both slender and stumpy forms of\n                  <jats:italic>T. brucei</jats:italic>\n                  . Furthermore,\n                  <jats:italic>in silico</jats:italic>\n                  predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic\n                  <jats:italic>\n                    Cx3cr1\n                    <jats:sup>+</jats:sup>\n                  </jats:italic>\n                  microglia and\n                  <jats:italic>\n                    Cd138\n                    <jats:sup>+</jats:sup>\n                  </jats:italic>\n                  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.\n                </jats:p>","journal":null,"year":null,"id":603066,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1546911,"name":"Praveena Chandrasegaran","orcid":null,"position":1,"is_corresponding":false},{"id":246991,"name":"Matthew C. Sinton","orcid":"0000-0003-1292-799X","position":2,"is_corresponding":false},{"id":1416819,"name":"Emma M. Briggs","orcid":"0000-0002-6740-8882","position":3,"is_corresponding":false},{"id":260444,"name":"Thomas D. Otto","orcid":"0000-0002-1246-7404","position":4,"is_corresponding":false},{"id":1546912,"name":"Rhiannon Heslop","orcid":null,"position":5,"is_corresponding":false},{"id":1546913,"name":"Calum Bentley-Abbot","orcid":null,"position":6,"is_corresponding":false},{"id":109801,"name":"Colin Loney","orcid":"0000-0002-0508-1781","position":7,"is_corresponding":false},{"id":264713,"name":"Luı́s de Lecea","orcid":"0000-0002-8921-5942","position":8,"is_corresponding":false},{"id":240232,"name":"Neil A. Mabbott","orcid":"0000-0001-7395-1796","position":9,"is_corresponding":false},{"id":231130,"name":"Annette MacLeod","orcid":"0000-0002-0150-5049","position":10,"is_corresponding":false},{"id":334343,"name":"Juan F. Quintana","orcid":"0000-0002-5092-5576","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronic\n                  <i>Trypanosoma brucei</i>\n                  infection","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite\n                  <jats:italic>Trypanosoma brucei</jats:italic>\n                  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\n                  <jats:italic>T. brucei</jats:italic>\n                  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 3\n                  <jats:sup>rd</jats:sup>\n                  ventricle. This coincides with the spatial localisation of both slender and stumpy forms of\n                  <jats:italic>T. brucei</jats:italic>\n                  . Furthermore,\n                  <jats:italic>in silico</jats:italic>\n                  predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic\n                  <jats:italic>\n                    Cx3cr1\n                    <jats:sup>+</jats:sup>\n                  </jats:italic>\n                  microglia and\n                  <jats:italic>\n                    Cd138\n                    <jats:sup>+</jats:sup>\n                  </jats:italic>\n                  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.\n                </jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":"https://openalex.org/W4220746028","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"209511","title":"The skin as a reservoir for trypanosomes: the key to understanding transmission and disease pathology"},{"funder_name":"Wellcome Trust","grant_id":"221640","title":"Molecular basis of parasite-induced disruption of host circadian outputs"},{"funder_name":"Wellcome Trust","grant_id":"218648","title":"Deciphering developmental commitment in African trypanosomes using single-cell transcriptomics"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2022,"count":3}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/03/28/2022.03.25.485502.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/03/28/2022.03.25.485502.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.03.25.485502","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.03.25.485502","host_type":"repository"},{"url":"https://research.manchester.ac.uk/en/publications/4e074e1c-16b4-457e-b745-cd4d4845551f","host_type":"repository"},{"url":"https://www.research.ed.ac.uk/en/publications/2a025eb1-4f28-4047-af23-f98105f60608","host_type":"repository"},{"url":"https://zenodo.org/record/6387555","host_type":"repository"},{"url":"http://dx.doi.org/10.1101/2022.03.25.485502","host_type":""},{"url":"https://zenodo.org/records/6387555","host_type":""},{"url":"https://hdl.handle.net/20.500.11820/2a025eb1-4f28-4047-af23-f98105f60608","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/259798757/2022.03.25.485502v2.full.pdf","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/259798760/2022.03.25.485502v2.full.pdf","host_type":""}],"fields_of_study":["Immune Cell Function and Interaction","Trypanosoma species research and implications","Neuroinflammation and Neurodegeneration Mechanisms","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Trypanosoma brucei","Biology","Neuroinflammation","Microglia","Crosstalk","African trypanosomiasis","Cell biology","Central nervous system","Transcriptome","Immunology","Heligmosomoides polygyrus","Neuroscience","Inflammation","Immune system","Trypanosomiasis","Genetics","Plasma cells","sleeping sickness","African trypanosomes","Single cell transcriptomics","Spatial transcriptomics","single cell RNA sequencing","spatial 30 transcriptomics"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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