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Altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni infection.

ABSTRACT: Altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni infection.

PROVIDER: PRJNA597049 | ENA |

REPOSITORIES: ENA

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Altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni infection.

Project description:Schistosomiasis increases the risk of HIV acquisition in women, by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or S. mansoni infection using mucosal gene expression and cervicovaginal lavage cytokine levels. We recruited women with/without S. haematobium and with/without S. mansoni infections from separate villages in rural Tanzania, as determined by urine and stool microscopy and serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. In the S. haematobium village, 110 genes were differentially expressed in the cervical mucosa of women with (n=18) versus without (n=39) S. haematobium. Among the 27 cytokines analyzed in cervicovaginal lavage fluids, interleukin 15 (IL-15) was lower in women with S. haematobium (62.8 versus 102.9 pg/mL, adjusted p=0.0013). Differences were not observed in the S. mansoni setting between women with (n=11) or without (n=29) S. mansoni. We demonstrate altered cervical mucosal gene expression and lower IL-15 levels in women with S. haematobium but not S. mansoni, which may impact HIV acquisition and cancer risks. Studies to determine effects of anti-schistosome treatment on these mucosal alterations are needed.

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Altered Cervical Mucosal Gene Expression and Lower Interleukin 15 Levels in Women With Schistosoma haematobium Infection but Not in Women With Schistosoma mansoni Infection.

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Project description:Schistosome worms infect over 200 million people worldwide. They live in the host’s bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active Schistosoma haematobium infection and to determine whether this signature differs between males and females. mRNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis (IPA) was used to identify gene networks altered in the presence of S. haematobium. We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially expressed genes between those with or without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with 1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. The top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of schistosome infection.

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