Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA750936 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T cell function, and CTLA-4 as a predicted regulator in these processes.
2022-02-21 | GSE181179 | GEO
Project description:We hypothesized that differential gene expression contributes to phenotypic variation of parasites which results in specific interaction of Plasmodium falciparum with its human host. In this study we used microarray hybridization to analyse the transcriptomes of P.falciparum isolated from asymptomatic carriers and from cerebral and uncomplicated malaria patients. We also investigated the transcriptomes of the 3D7 clone and the selected 3D7-Lib line.
2014-12-01 | E-MTAB-2139 | biostudies-arrayexpress
Project description:Background: Malaria is a public health problem in parts of Thailand, where Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In the northwestern border province of Tak parasite prevalence is now estimated to be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low-level parasitaemia. The objective of this study was to assess the current epidemiology of falciparum and vivax malaria in Tak using molecular methods to detect exposure to and infection with parasites; in particular, the prevalence of asymptomatic infections and infections with submicroscopic parasite levels. Methods: Three-hundred microlitres of whole blood from finger-prick were collected into capillary tubes from residents of a sentinel village and from patients at a malaria clinic. Pelleted cellular fractions were screened by quantitative PCR to determine parasite prevalence, while plasma was probed on a protein microarray displaying hundreds of P. falciparum and P. vivax proteins to obtain antibody response profiles in those individuals. Results: Of 219 samples from the village, qPCR detected 25 (11.4%) Plasmodium sp. infections, of which 92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic patients, 27 (44.3%) were positive by qPCR, of which 25.9% had submicroscopic parasite levels. Cryptic mixed infections, misdiagnosed as single-species infections by microscopy, were found in 7 (25.9%) malaria patients. All sample donors, parasitaemic and non-parasitaemic alike, had serological evidence of parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens significantly associated with asymptomatic infections were P. falciparum MSP2, DnaJ protein, putative E1E2 ATPase, and three others.
2014-06-22 | GSE55265 | 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
Project description:During the dry season, in many African regions, persistent asymptomatic malaria cases have been linked to downregulated virulence gene expression encoded by the var gene family, resulting in low adhesion and increased circulation time of Plasmodium falciparum-infected erythrocytes 1. Several studies have investigated associations between parasite transcription and clinical severity, but the underlying process that results in lower virulence gene expression in asymptomatic malaria remains unknown. Here we report an RNA Polymerase III-dependent mechanism that in response to external stimuli, decreases var gene transcription and parasite multiplication rate. The singular expression of var gene members, while under tight epigenetic regulation by the parasite 2, is additionally controlled by a family of ncRNA, termed RUF6 3. We show that Pol III transcription of tRNAs and RUF6 is severely decreased in field isolates of asymptomatic individuals infected with P. falciparum during the dry season. We identified Maf1 as a negative effector of RUF6 ncRNA transcription and show that external stimuli depend on plasmodial Maf1 to trigger lower expression of RNA Pol III-transcribed genes. Our results uncover a TOR-independent unprecedented signaling pathway in a protozoan pathogen that is highly relevant for establishing asymptomatic subclinical parasite persistence in the dry season.
2024-06-25 | PXD040576 | Pride
Project description:Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate maintenance of chronic symptomless infections that sustain malaria transmission. Here, we have determined the gene expression profiles of the parasite population and the corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (<15 years). We compared children who were defined as uninfected, asymptomatic and those with febrile malaria. Children with asymptomatic infections had a parasite transcriptional profile characterized by a bias toward trophozoite stage (~12 hours-post invasion) parasites and low parasite levels, while earlier ring stage parasites were characteristic of febrile malaria. The host response of asymptomatic children was characterized by downregulated transcription of genes associated with inflammatory responses, compared with children with febrile malaria, which may lead to less cytoadherence of more mature parasite stages. Interestingly, the host responses during febrile infections that followed an asymptomatic infection featured stronger inflammatory responses, whereas the febrile host responses from previously uninfected children featured increased humoral immune responses. The priming effect of prior asymptomatic infection may explain the blunted acquisition of antibody responses seen to malaria antigens following natural exposure or vaccination in malaria endemic areas.
2024-02-14 | GSE240643 | GEO
Project description:Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. However, there is limited information on how host-parasite interactions mediate maintenance of chronic symptomless infections that sustain malaria transmission. In this study, we identified uninfected and asymptomatic individuals and followed them until they manifested with symptoms of fever in the presence of malaria parasites and compared the gene expression profiles of peripheral blood mononuclear cells (PBMCs). The host response of asymptomatic children was characterized by downregulation of genes associated with inflammatory responses, compared to uninfected children and children with febrile malaria. They did show greater expression of some genes associated with the humoral response compared to uninfected children. Interestingly, the host responses during febrile infections that followed an asymptomatic infection featured stronger inflammatory responses, whereas the febrile host responses from previously uninfected children featured increased humoral immune responses.
2024-02-14 | GSE241467 | GEO
Project description:Replication origin mapping in the malaria parasite Plasmodium falciparum
2022-08-04 | GSE210010 | GEO
Project description:The mRNA 5â² cap is normally essential for eukaryotic mRNA translation, stabilization and transport and both the cap and eIF4E are important elements of post-transcriptional gene regulation. To further our understanding of mRNA translation in the human malaria parasite Plasmodium falciparum, we have investigated the parasite translation initiation factor eIF4E and its interaction with 5â² capped mRNA. We have purified P. falciparum eIF4E as a recombinant protein and demonstrated that it has canonical mRNA 5â² cap binding activity. We used this protein to purify P. falciparum full-length 5â² capped mRNAs from total parasite RNA. Microarray analysis comparing total and eIF4E-purified 5â² capped mRNAs shows that a subset of 34 features were more than two-fold under-represented in the purified RNA sample, including 19 features representative of nuclear transcripts. The uncapped nuclear transcripts may represent a class of mRNAs targeted for storage and cap removal. Keywords: total RNA vs purified capped mRNA The microarray data were obtained from four hybridizations using RNA from two independent GST-PfeIF4E purifications from separate malaria cultures.
2010-06-10 | E-GEOD-6356 | biostudies-arrayexpress
Project description:Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.
| S-SCDT-MSB-2021-10824 | biostudies-other