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Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory.
Soon, Megan S F; Lee, Hyun Jae; Engel, Jessica A; Straube, Jasmin; Thomas, Bryce S; Pernold, Clara P S; Clarke, Lachlan S; Laohamonthonkul, Pawat; Haldar, Rohit N; Williams, Cameron G; Lansink, Lianne I M; Moreira, Marcela L; Bramhall, Michael; Koufariotis, Lambros T; Wood, Scott; Chen, Xi; James, Kylie R; Lönnberg, Tapio; Lane, Steven W; Belz, Gabrielle T; Engwerda, Christian R; Khoury, David S; Davenport, Miles P; Svensson, Valentine; Teichmann, Sarah A; Haque, Ashraful.
Afiliação
  • Soon MSF; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Lee HJ; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Engel JA; Department of Microbiology and Immunology, University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
  • Straube J; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Thomas BS; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Pernold CPS; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Clarke LS; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Laohamonthonkul P; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Haldar RN; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Williams CG; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Lansink LIM; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Moreira ML; Department of Microbiology and Immunology, University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
  • Bramhall M; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Koufariotis LT; Department of Microbiology and Immunology, University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
  • Wood S; Department of Microbiology and Immunology, University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
  • Chen X; Department of Microbiology and Immunology, University of Melbourne, located at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
  • James KR; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Lönnberg T; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Lane SW; Department of Biology, South University of Science and Technology of China, Shenzhen, China.
  • Belz GT; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Engwerda CR; Cavendish Laboratory, University of Cambridge, Cambridge, UK.
  • Khoury DS; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Davenport MP; Cavendish Laboratory, University of Cambridge, Cambridge, UK.
  • Svensson V; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
  • Teichmann SA; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Haque A; The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.
Nat Immunol ; 21(12): 1597-1610, 2020 12.
Article em En | MEDLINE | ID: mdl-33046889
The dynamics of CD4+ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4+ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (TH1) and follicular helper T (TFH) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated TH1 and TFH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between TFH and central memory were revealed, with antimalarials modulating these responses and boosting TH1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4+ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium / Linfócitos T CD4-Positivos / Transcriptoma / Memória Imunológica / Malária Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium / Linfócitos T CD4-Positivos / Transcriptoma / Memória Imunológica / Malária Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article