Published October 15, 2025 | Version 1
Dataset Open

Dataset: Memory Regulatory T Cells Reprogram into Protective Tfh-like Effectors in Recurrent Malaria

Authors/Creators

  • 1. EDMO icon The University of Georgia
  • 2. University of Georgia
  • 3. Center for Tropical and Emerging Global Diseases
  • 4. US National Institutes of Health
  • 5. Mali International Centre of Excellence in Research
  • 6. ROR icon National Institutes of Health

Contributors

Project leader:

  • 1. University of Georgia

Description

Although people living in malaria-endemic areas experience repeated infections with Plasmodium, the role of regulatory T cells (Tregs) in recurrent malaria remains poorly understood. During a primary infection with Plasmodium, Tregs suppress protective immunity by inhibiting germinal center (GC) reactions, thereby impeding the control of parasitemia. In contrast, we demonstrate here that memory Tregs (mTregs) remaining after the clearance of initial Plasmodium infection acquire protective functions upon recall. Relying on longitudinal studies in humans and mice, we show that mTregs undergo antigen-driven expansion and inflammation-induced epigenetic reprogramming during reinfection to transition from Foxp3+ immunosuppressive cells to Bcl6+ follicular T helper (Tfh)-like effectors. These mTreg-derived Tfh-like cells enhance GC responses and the generation of Plasmodium-specific antibodies, ultimately facilitating Plasmodium control. Precluding such mTreg-to-Tfh differentiation abolished protection. Our findings reveal a previously unrecognized adaptive plasticity in canonical mTregs that enables a context-dependent functional switch from immunoregulatory to protective effectors during recurrent infections.

Notes

The repository is associated with Charles-Chess et al. (2026), Nature Immunology manuscript # NI-A41630B

The repository contains: (1) the raw data associated with the DNA methylation and single-cell transcriptomic experiments performed in the study; (2) the analysis pipelines (markdown/html) used; and, (3) the .rds outputs.

For users who would like access to the .fastq files, we direct you to the NCBI's short read archive (SRA), BioProject code: PRJNA1276081.

Files

methyl-seq-analysis-files.zip

Files (10.2 GB)

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md5:80ac987ac081e0b547326f61a2e665ed
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md5:8c9a3d3f67eb025ae621234333e260de
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md5:6374cff4d2856a32d07ba9e9c87422ce
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Additional details

Additional titles

Subtitle
Data files and scripts associated with the processing and analysis of 'omics data from nTregs, mTreg and xTregs

Funding

National Institutes of Health
Type-I Interferons drive cell-autonomous immunity to malaria 5R01AI168307-03
National Institutes of Health
Memory Regulatory T cells in Recurring Malaria AI193123-01
National Institutes of Health
State of the ART: Functional genomics of RNA-binding proteins and their role in artemisinin drug resistance in Plasmodium falciparum 1K99AI177948-01A1