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Related Experiment Video

Updated: Nov 25, 2025

An In Vitro Model for Measuring Immune Responses to Malaria in the Context of HIV Co-infection
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Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes.

Jona Walk1,2, Farid Keramati3, L Charlotte J de Bree2,4,5

  • 1Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

Frontiers in Molecular Biosciences
|December 16, 2020
PubMed
Summary

Malaria infection can train monocytes, enhancing their immune memory. This trained immunity, observed 36 days post-infection, has an epigenetic basis, reprogramming monocytes long after parasite clearance.

Keywords:
CHMIChIP-seqRNA-seqepigeneticsinnate immunitymalariatrained immunity

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Epigenetics

Background:

  • Trained immunity, a form of innate immune memory, is known after BCG vaccination and in vitro stimuli.
  • The capacity of clinical infections, like malaria, to induce trained immunity remained uncertain.

Purpose of the Study:

  • To investigate if Plasmodium falciparum infection induces trained immunity in human monocytes.
  • To explore the epigenetic mechanisms underlying infection-induced trained immunity.

Main Methods:

  • Controlled Human Malaria Infection (CHMI) model in five volunteers.
  • Measurement of monocyte-derived cytokine production (IL-6, TNF-α).
  • Transcriptomic and epigenomic analyses (H3K4me3) of monocytes.

Main Results:

  • Monocytes showed reduced inflammatory cytokine production during acute malaria.
  • A significant increase in IL-6 and TNF-α production was observed 36 days post-malaria infection.
  • Monocytes exhibited long-term epigenetic reprogramming (H3K4me3 changes) in inflammatory genes.

Conclusions:

  • Plasmodium falciparum infection induces a trained immunity phenotype in human monocytes.
  • Epigenetic modifications provide a molecular basis for malaria-induced trained immunity in vivo.
  • Trained immunity may have long-term implications for immune responses following malaria.