Metabolome modulation of the host adaptive immunity in human malaria.

Nature Metabolism
Wael AbdrabouYoussef Idaghdour

Abstract

Host responses to infection with the malaria parasite Plasmodium falciparum 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...Continue Reading

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Citations

Jun 12, 2021·Nature Metabolism·Malcolm J McConville, Christian R Engwerda
Jun 25, 2021·Nature Reviews. Immunology·Kirsty Minton

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Methods Mentioned

BETA
FACS
PCR
RNA-seq
metabolomic profiling
genotyping
flow cytometry
flow
PCA

Software Mentioned

ClueGo
STAR
MetaboAnalyst
JMP Genomics
bcl2fastq
Ensembl
SPSS PROCESS model
mediation
FastQC
Trimmomatic

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