Metabolome modulation of the host adaptive immunity in human malaria

Wael Abdrabou, Mame Massar Dieng, Aïssatou Diawara, Samuel Sindié Sermé, Dareen Almojil, Salif Sombié, Noelie Bere Henry, Désiré Kargougou, Vinu Manikandan, Issiaka Soulama, Youssef Idaghdour

Research output: Contribution to journalArticlepeer-review

Abstract

Host responses to infection with the malaria parasite Plasmodiumfalciparum vary among individuals for reasons that are poorly understood. Here we reveal metabolic perturbations as a consequence of malaria infection in children and identify an immunosuppressive role of endogenous steroid production in the context of P. falciparum infection. We perform metabolomics on matched samples from children from two ethnic groups in West Africa, before and after infection with seasonal malaria. Analysing 306 global metabolomes, we identify 92 parasitaemia-associated metabolites with impact on the host adaptive immune response. Integrative metabolomic and transcriptomic analyses, and causal mediation and moderation analyses, reveal an infection-driven immunosuppressive role of parasitaemia-associated pregnenolone steroids on lymphocyte function and the expression of key immunoregulatory lymphocyte genes in the Gouin ethnic group. In children from the less malaria-susceptible Fulani ethnic group, we observe opposing responses following infection, consistent with the immunosuppressive role of endogenous steroids in malaria. These findings advance our understanding of P. falciparum pathogenesis in humans and identify potential new targets for antimalarial therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)1001-1016
Number of pages16
JournalNature Metabolism
Volume3
Issue number7
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology
  • Physiology (medical)

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