Transcriptome analysis of peripheral blood ofSchistosoma mansoniinfected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology

Abstract

AbstractOver 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of allSchistosomaspecies. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10 - 15 years with varying intensities ofSchistosoma mansoniinfection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44S. mansoniinfected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. Principal component analysis revealed clustering of gene expression by gender whenS. mansoniinfected children were compared with uninfected children. In addition, we identified 14 DEGs betweenS. mansoniinfected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis inS. mansoniinfection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronicS. mansoniinfection is a stealth infection that does not stimulate a strong immune response.Author SummarySchistosomiasis is a neglected tropical disease transmitted via an intermediate snail host through contact with contaminated fresh water. Even with routine Mass Drug Administration for treatment of the infection, re-infections are still common and variations in infection intensity and pathology are still observed in individuals in the same location. These may be due to differences in individuals’ response toS. mansoniinfection. In this study, we used RNAseq to identify differentially expressed genes associated withS. mansoniinfection in children between 10-15 years. We conducted comparisons between phenotypes including infection intensities measured by circulating anodic antigen, wasting by body mass index and stunting by height-for-age z score. Our data showed very low numbers of significant differentially expressed genes in all comparisons. Some of the few differentially expressed genes that were observed were associated with fibrosis which is the cause of pathology in humans and has been observed in late stages ofS. mansoniinfection in murine studies.