Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory

Soon，Megan S.F.1; Lee，Hyun Jae1,2; Engel，Jessica A.1; Straube，Jasmin1; Thomas，Bryce S.1; Pernold，Clara P.S.1; Clarke，Lachlan S.1; Laohamonthonkul，Pawat1; Haldar，Rohit N.1; Williams，Cameron G.1,2; Lansink，Lianne I.M.1,2; Moreira，Marcela L.2; Bramhall，Michael2; Koufariotis，Lambros T.1; Wood，Scott1; Chen，Xi3,4,5; James，Kylie R.4,5; Lönnberg，Tapio6; Lane，Steven W.1; Belz，Gabrielle T.7,8,9; Engwerda，Christian R.1; Khoury，David S.10; Davenport，Miles P.10; Svensson，Valentine11; Teichmann，Sarah A.4,5; Haque，Ashraful1,2

2020

10.1038/s41590-020-0800-8

NATURE IMMUNOLOGY   影响因子和分区

1529-2908

1529-2916

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 (T1) and follicular helper T (T) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T1 and T trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T and central memory were revealed, with antimalarials modulating these responses and boosting T1 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/).

SCI

英语

NI论文

其他

Australian National Health & Medical Research Council[1126399]

Immunology

Immunology

WOS:000577043300001

NATURE RESEARCH

IMMUNOLOGY

2-s2.0-85092394510

Scopus

1.QIMR Berghofer Medical Research Institute,Herston,Brisbane,Australia
2.Department of Microbiology and Immunology,University of Melbourne,located at The Peter Doherty Institute for Infection and Immunity,Parkville,Australia
3.Department of Biology,South University of Science and Technology of China,Shenzhen,China
4.Wellcome Sanger Institute,Wellcome Genome Campus,Hinxton,United Kingdom
5.Cavendish Laboratory,University of Cambridge,Cambridge,United Kingdom
6.Turku Bioscience Centre,University of Turku and Åbo Akademi University,Turku,Finland
7.The University of Queensland Diamantina Institute,The University of Queensland,Brisbane,Australia
8.Walter and Eliza Hall Institute of Medical Research,Parkville,Australia
9.Department of Medical Biology,University of Melbourne,Parkville,Australia
10.Kirby Institute,University of New South Wales,Kensington,Sydney,Australia
11.Division of Biology and Biological Engineering,California Institute of Technology,Pasadena,United States

Soon，Megan S.F.,Lee，Hyun Jae,Engel，Jessica A.,et al. Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory[J]. NATURE IMMUNOLOGY,2020,21(12):1597-+.

Soon，Megan S.F..,Lee，Hyun Jae.,Engel，Jessica A..,Straube，Jasmin.,Thomas，Bryce S..,...&Haque，Ashraful.(2020).Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory.NATURE IMMUNOLOGY,21(12),1597-+.

Soon，Megan S.F.,et al."Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory".NATURE IMMUNOLOGY 21.12(2020):1597-+.