Transcriptome dynamics of CD4( ) T cells during malaria maps gradual transit from effector to memory
Megan SF Soon, Hyun Jae Lee, Jessica A Engel, Jasmin Straube, Bryce S Thomas, Clara PS Pernold, Lachlan S Clarke, Pawat Laohamonthonkul, Rohit N Haldar, Cameron G Williams, Lianne IM Lansink, Marcela L Moreira, Michael Bramhall, Lambros T Koufariotis, Scott Wood, Xi Chen, Kylie R James, Tapio Lonnberg, Steven W Lane, Gabrielle T Belz Show all
NATURE IMMUNOLOGY | NATURE RESEARCH | Published : 2020
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 betwee..View full abstract
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Awarded by Australian National Health & Medical Research Council
This study was funded by the Australian National Health & Medical Research Council: Project Grant 1126399 (awarded to A.H. and S.A.T.). Smart-seq2 work was funded by ERC Consolidator grant ThDEFINE (awarded to S.A.T.). We are grateful to J. Moehrle at Medicines for Malaria Venture for providing sodium artesunate. We acknowledge the expertise and assistance of several QIMR Berghofer Medical Research Institute Core Staff: the Flow Cytometry and Microscopy Core, particularly M. Rist and T. Hong Nguyen, for single-cell sorting; the Histology Core, including C. Winterford; the Animal Facility, including all technicians involved with animal husbandry; the Next-Generation-Sequencing Core, including P. Collins for assistance with droplet-based scRNA-seq and Illumina sequencing. We acknowledge the Single-Cell Genomics Core Facility and sequencing pipeline at the Wellcome Sanger Institute for plate-based Smart-seq2 and scATAC-seq processing.