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

Autor: Ashraful Haque, Lachlan S. Clarke, Scott Wood, Kylie R. James, Xi Chen, Jessica A. Engel, Lianne I. M. Lansink, David S. Khoury, Valentine Svensson, Megan S. F. Soon, Pawat Laohamonthonkul, Clara P. S. Pernold, Steven W. Lane, Hyun Jae Lee, Bryce S. Thomas, Tapio Lönnberg, Jasmin Straube, Marcela de Lima Moreira, Gabrielle T. Belz, Rohit N. Haldar, Christian R. Engwerda, Cameron G. Williams, Michael Bramhall, Miles P. Davenport, Lambros T. Koufariotis, Sarah A. Teichmann
Rok vydání: 2020
Předmět:
Zdroj: Nature Immunology
ISSN: 1529-2908
DOI: 10.1038/s41590-020-0800-8
Popis: 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 (T_H1) and follicular helper T (T_(FH)) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T_H1 and T_(FH) trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T_(FH) and central memory were revealed, with antimalarials modulating these responses and boosting T_H1 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/).
Databáze: OpenAIRE
Externí odkaz: