Longitudinal profiling of the human immune response to Plasmodium falciparum
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132050 | GEO | 2020/09/07
REPOSITORIES: GEO
Similar Datasets
Project description:We took a systems immunology approach to analyse the evolution of the human immune response to the first three infections of life in a re-challenge model of falciparum malaria. Ten volunteers were infected up to three times with Plasmodium falciparum in 4- to 8-month intervals. Remarkably, parasite densities and the dynamics of blood-stage infection were not altered over the course of three homologous infections. To track the development of immunity in real-time we used whole blood RNA-sequencing to analyse each volunteer’s transcriptional response throughout infection and convalescence (up to 9 time points per volunteer per infection).
2021-05-25 | GSE172450 | GEO
Project description:The objective of this study is to characterize the overall transcriptome of P. falciparum NF54 derived from a controlled-human malaria infection (CHMI) study. Healthy, immunologically naïve human volunteers were infected intradermally or intravenously with different dosages of Plasmodium falciparum sporozoites (Sanaria® PfSPZ Challenge). Parasites were isolated from these volunteers and subjected to a range of in vitro culture generation prior to RNA collection.
2019-08-21 | GSE136076 | GEO
Project description:<p>Description:<br/> Experimental exposure to malaria parasites can lead to development of protective immunity, providing a foothold for the development of a malaria vaccine. The goal of this study is to investigate immune transcriptional profiles associated with malaria protective immune responses induced by experimental Chemo-Prophylaxis and Sporozoites (CPS) immunization of P. <i>falciparum</i>-naive human volunteers. Samples for this study were obtained from a CPS-immunization study conducted in 2011 (ClinicalTrials.gov Identifier: NCT01218893), where healthy volunteers received CPS-immunization with bites from different numbers of P. <i>falciparum</i>-infected mosquitoes (three times 15 (n=5), 10 (n=9) or 5 (n=10)). Five control subjects received uninfected mosquito bites under chloroquine prophylaxis. Fifteen weeks after discontinuation of chloroquine prophylaxis, all volunteers were challenged by exposure to infected mosquito bites. </p> <p>Study Design:<br/> A maximum of 30 volunteers were divided into four groups. All volunteers received weekly chloroquine prophylaxis for a period of 13 weeks (91 days). During these 13 weeks, on days 8, 36 and 64 they were exposed to the bites of 15 mosquitoes. Group 1 (n=5, positive control) received three CPS immunizations by 15 mosquitoes infected with P. falciparum sporozoites. Group 2 (n=10) received three times 10 bites from infected mosquitoes and 5 bites from uninfected mosquitoes. Group 3 (n=10) received three times 5 bites from infected mosquitoes and 10 bites from uninfected mosquitoes. Group 4 (n=5), the negative control, received three placebo immunizations with 15 bites of uninfected mosquitoes. Fifteen weeks after discontinuation of chloroquine prophylaxis, all 30 volunteers were challenged at day 196 by the bites of 5 infectious mosquitoes and followed for 21 days. All subjects were treated with chloroquine 21 days after challenge or whenever they had a positive thick smear during that period. </p>
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Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle Examination of polyA selected RNA in Plasmodium falciparum 3D7 strain at 8 different stages using RNA-seq
2010-10-28 | E-GEOD-23865 | biostudies-arrayexpress
Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle
2010-10-28 | GSE23865 | GEO
Project description:The regulation of immune cell responses to infection is a complex process that involves various molecular mechanisms, including epigenetic regulation. DNA methylation has been shown to play central roles in regulating gene expression and modulating cell response during infection. However, the nature and extent to which DNA methylation is involved in the host immune response in human malaria remains unknown. Here, we present a longitudinal study investigating the temporal dynamics of genome-wide in vivo DNA methylation profiles using 189 MethylationEPIC 850K profiles from 66 children in Burkina Faso, West Africa, sampled three times: before infection, during symptomatic parasitemia, and after malaria treatment. The results revealed major changes in the DNA methylation profiles of children in response to both Plasmodium falciparum infection and malaria treatment, with widespread hypomethylation of CpGs upon infection (82% of 6.8K differentially methylated regions). We document a remarkable reversal of CpG methylation profiles upon treatment to pre-infection states. These changes implicate divergence in core immune processes, including the regulation of lymphocyte, neutrophil, and myeloid leukocyte function. Integrative DNA methylation-mRNA analysis of a top differentially methylated region overlapping the pro-inflammatory gene TNF implicates DNA methylation of TNF cis regulatory elements in the molecular mechanisms of TNF regulation in human malaria. Our results highlight a central role of epigenetic regulation in mounting the host immune response to Plasmodium falciparum infection and in response to malaria treatment.
2023-06-08 | GSE230850 | GEO
Project description:This experiment characterizes the localisation of H2A.Z, H3K9ac and H3K4me3 in the epigenome of the human malaria parasite, P. falciparum at 4 different stages of intraerythrocytic development.
2010-10-28 | GSE23867 | GEO
Project description:Controlled human malaria infection is a powerful experimental medicine tool to understand the human immune response to a first ever malaria infection. Here we have taken this approach a step further and conducted the first human malaria reinfection trial in the modern era. Volunteers were challenged up to three times with Plasmodium falciparum in 4- to 8-month intervals. Remarkably, parasite densities and the dynamics of blood-stage infection were not altered over the course of three homologous infections. Using whole blood RNA-sequencing we tracked the host immune response through time and found that the emergency myeloid response, which triggers systemic inflammation and the global recruitment of T cells into lymphoid tissues, is not altered by repeated infection. Six days after parasite clearance, when the innate response subsides, T cells return to the circulation and reflect the outcome of critical cell-cell interactions within the inflamed spleen. By transcriptionally profiling flow sorted CD4+ T cell subsets after their release from the tissue we could show that TH1 polarised effector response in naïve hosts is tolerised upon re-challenge to avoid collateral tissue damage. Instead, a subset of specialised cytokine-producing CD4+ T cells are activated to promote essential protective immune functions. Together these data indicate that innate and adaptive immune responses can be uncoupled in malaria and illustrate that human hosts prioritises damage limitation (tolerance) over parasite clearance (resistance) to quickly acquire clinical immunity.
2021-05-25 | GSE172481 | GEO
Project description:The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased efficiency of splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.
2020-08-20 | GSE148125 | GEO