Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101038 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29203307_1.fastq.gz | Fastqsanger.gz | |||
| SRR29203307_2.fastq.gz | Fastqsanger.gz | |||
| SRR29203308_1.fastq.gz | Fastqsanger.gz | |||
| SRR29203308_2.fastq.gz | Fastqsanger.gz | |||
| SRR29203821_1.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptomics of malaria susceptibility in Malian children
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Project description:In malaria-naïve individuals, P. falciparum (Pf) infection results in numerous Pf-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, repeatedly infected individuals in endemic areas are often asymptomatic and have low levels of iRBCs, even children who have yet to acquire reliably protective antibodies. The molecular mechanisms underlying these clinical observations are unclear. PBMCs collected from Malian children before the malaria season responded to iRBCs by producing pyrogenic, pro-inflammatory mediators such as IL-1β, IL-6 and TNF. However, following febrile malaria there was a marked shift in the response to iRBCs with the same children's PBMCs producing lower levels of those cytokines. These data suggest that malaria-induced epigenetic reprogramming of innate immune cells may play a role in immunity to malaria. Accordingly, age-stratified analysis of monocytes collected before the malaria season showed an inverse relationship between age and pro-inflammatory cytokine production capacity.
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Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season.
2017-01-01 | GSE86308 | GEO
Project description:Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. To identify determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing, we analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. We also observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. This suggests that differences in apoptotic and inflammatory gene expression patterns can predict susceptibility to clinical malaria.
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Project description:Gammadelta T cells from Ugandan children were tested for their responsiveness to stimulation with malaria parasites. Independent PBMC samples from children were incubated with Plasmodium falciparum-infected red blood cells for 6 h post-treatment, and Vdelta2+ gammadelta T cells were double sorted by FACS directly into an RNA lysis buffer. RNA was isolated, amplified using 2 rounds of linear amplification, and hybridized to Agilent Human 8x60k microarrays as a single color experiment.
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Project description:We aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co). Understanding malarial immunopathology in the human host represents and enormous challenge for transcriptomic research. In this work, we used microarray and real-time RT-PCR technology to pursue deeper knowledge about the mechanisms underlying this disease in African children. To this end, we investigated the genomic transcriptional profiles in whole blood of healthy children and children with asymptomatic infection, uncomplicated malaria, malaria associated with severe anemia and cerebral malaria and compared them with previously published microarray results. We were able to discriminate between the different presentations of P. falciparum infection using supervised and unsupervised clustering of microarray data and unsupervised double-hierarchical clustering of real-time RT-PCR results of a set of 22 genes known to be expressed in at least one of the principal blood cell lineages. We further found considerable overlap between genes regulated in Kenyan and Gabonese children with symptomatic malaria, in contrast to adults with acute malaria from Cameroon. Different signatures for transcription factor binding sites in promoters of genes either up-regulated in symptomatic disease, specifically up-regulated in uncomplicated malaria or specifically down-regulated in cerebral malaria point out that similar gene expression in each of these clinical presentations is probably a result of common regulation at the transcriptional level. Immunoglobulin production, complement regulation and IFN beta signalling emerged as most discrepant features between uncomplicated malaria and all other investigated presentations, correlating with IRF7 and ISRE binding signatures in the corresponding genes. Down-regulation of several genes in cerebral malaria seems instead to be a response to hypoxia orchestrated by AhRF, GABP and HIF1 transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia and inversely with hemoglobin concentration and should be evaluated as prognostic markers to direct early therapeutic measures and prevent malarial disease evolution and death.
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