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Mechanisms of immune evasion in P. falciparum malaria revealed by integrative gene expression profiling [miRNA]

ABSTRACT: We performed a genome-wide profiling of miRNAs and mRNA, DNA sequencing of human whole blood sample to identify miRNAs responsive to P.falciparum (P.f) infection and/or associated with parasite load. We identified a set of 72 miRNAs that are positively or negatively associated with parasitemia. We also performed expression quantitative trait loci of miRNAs(miR-eQTL) of P.f infected individuals. The miR-eQTL dataset allowed us to determine relevant genetic variant responsible for miRNAs expression differences between P.f infected individuals and find novel malaria-associated miRNAs

ORGANISM(S): Homo sapiens

PROVIDER: GSE144413 | GEO | 2020/09/05

REPOSITORIES: GEO

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Project description:Co-infection with soil transmitted helminths (STH) and Plasmodium spp. parasites is a common occurrence in tropical developing countries, but the consequences of this interaction remain poorly understood. Here, we performed a multi-omic analysis on the peripheral blood and fecal samples of 130 individuals in Tierralta, Córdoba, Colombia who were infected with P. vivax alone (n = 33), co-infected with P. vivax and STH (n = 27), infected with STH alone (n = 39) or were infected with neither P. vivax nor STH (n = 31). In addition to Complete Blood Count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by RNA-Seq, fecal microbial communities were determined by 16S ribosomal RNA gene sequencing and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts were driven primarily by P. vivax infection, including an increased percentage of neutrophils that was associated with a transcriptional signature of neutrophil activation in the blood. P. vivax infection was also associated with increased levels of IL-6, IL-8 and IL-10 and these cytokine levels were not affected by STH co-infection. Surprisingly, P. vivax infection was more strongly associated with changes in the microbiome than STH infection. Children infected with P. vivax exhibited elevated Bacteroides and reduced Prevotella and Clostridiaceae, but these differences were not observed in individuals co-infected with STH. We also observed that P. vivax parasitemia is higher in STH-infected population. When we used machine learning to identify the most important predictors of P. vivax parasite burden from all measured variables, bacterial taxa were the strongest predictors of parasitemia levels in P. vivax infected individuals. In contrast, circulating TGF- β was identified as the strongest predictor of T. trichiura egg burden. This study provides unexpected evidence that the gut microbiota may have a stronger link with P. vivax than with STH infection.

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Mechanisms of immune evasion in P. falciparum malaria revealed by integrative gene expression profiling [miRNA]

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