Plasmodium falciparum increased time in circulation underlies persistent asymptomatic infection in the dry season
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ABSTRACT:
PROVIDER: PRJNA623299 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11486400_1.fastq.gz | Fastqsanger.gz | |||
| SRR11486400_2.fastq.gz | Fastqsanger.gz | |||
| SRR11486401_1.fastq.gz | Fastqsanger.gz | |||
| SRR11486401_2.fastq.gz | Fastqsanger.gz | |||
| SRR11486402_1.fastq.gz | Fastqsanger.gz |
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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: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 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.
2020-05-25 | ST001384 | MetabolomicsWorkbench
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:Soil samples Metagenome Dry Season Metagenome
| PRJNA875082 | ENA
Project description:The mechanisms by which mosquitoes survive the desiccating conditions of the dry season in West African savannahs and are able to readily transmit malaria as soon as the rains start remain largely unknown. Thus, we examined the degree to which the physiology of 1 h- and 24 h-old female An. gambiae M and S is altered at the onset of the dry season (“ods”) by examining their metabolic fingerprints and protein expression, which were compared to those of females exposed to the rainy season (“rs”) conditions. Three amino acids (phenylalanine, tyrosine and valine) that play a pivotal role in cuticle hardness were significantly decreased from the 1 h- to 24 h-old females, regardless of the experimental conditions. These amino acids were present in higher amounts in 1 h-old female An. gambiae M reared under “ods”; such a seasonal difference was not reported in the female S molecular form. Together with the increased expression of cuticular proteins 70 and 117(spots 67 and 65, respectively), our data suggest that the cuticle thickness, rigidity and permeability were adjusted at the onset of the dry season. Evident signs of energetic metabolism adjustments were found in both of the molecular forms at the onset of the dry season. Moreover, 1 h-old females of An. gambiae S were characterised by elevated amounts of glycogen phosphorylase, isocitrate dehydrogenase and citrate synthase, suggesting an increase of their metabolic activity at the onset of the dry season. This study presents novel insights into drought resistance in the mosquitoes of utmost medical importance.
2014-09-03 | PXD000294 | Pride
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.
2021-03-18 | GSE151116 | GEO
Project description:Anopheles gambiae mosquitoes play an important role in malaria transmission. In sub-Saharan Africa, the dry season can last several months. The mechanisms for mosquito population to survive through the dry season are poorly understood. One possible mechanism is that adults increase their desiccation tolerance over the dry season. Genetic analyses have shown that inversions 2La, 2Rb, 2Rc, 2Rd and 2Ru are associated with aridity resistance, however little is known about the transcriptional response of genes in response to desiccation. The results of the present study demonstrate that desiccation affects expression of genes associated with several mosquito physiological mechanisms, including those that protect against water loss, but all structural related genes decreased their expression. The identified differentially expressed genes in response to desiccation stress can lay a foundation for better understanding of molecular mechanisms underling dry-season survival of An. gambiae mosquitoes, so it may provide a different option for malaria vector control.
2011-12-31 | GSE25433 | GEO
Project description:Bicyclus anynana butterflies were reared at 17°C and 27°C to produce the dry and wet season forms. RNA was extracted using TRIzol from the heads of 12 individual animals ~0-3 hours after eclosing; 3 dry season females, 3 wet season females, 3 dry season males, and 3 wet season males. A TruSeq RNA Sample Preparation Kit v2 was used to make 12 double stranded cDNA libraries from polyadenylated RNA. We size selected for DNA at ~280-340 bp. Libraries were sequenced using a HiSeq 2500, paired end 100-cycle sequence run.
2015-10-01 | E-MTAB-3887 | biostudies-arrayexpress
Project description:BackgroundImmunity to the antigenically diverse parasite Plasmodium falciparum is acquired gradually after repeated exposure. Studies in areas of high malaria transmission have shown that asymptomatic individuals infected with multiclonal infections are at reduced risk of febrile malaria during follow-up.MethodsWe assessed the relationship between the genetic diversity of clones in P. falciparum infections that persist through the dry season and the subsequent risk of febrile malaria in 225 individuals aged 2-25 years in Mali, where the 6-month malaria and dry seasons are sharply demarcated. Polymerase chain reaction-based genotyping of the highly polymorphic merozoite surface protein 2 gene was performed on blood samples collected at 5 cross-sectional surveys.ResultsIn an age-adjusted analysis, individuals with multiclonal P. falciparum infections before the rainy season were at reduced risk of febrile malaria, compared with individuals who were uninfected (hazard ratio [HR], 0.28; 95% confidence interval [CI], .11-.69). In contrast, there was no significant association between risk of malaria and having 1 clone at baseline (HR, 0.71; 95% CI, .36-1.40).ConclusionsThe results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection.
| S-EPMC4539894 | biostudies-literature
Project description:This series represents the analysis of a commercial dry active yeast (purchased locally). The genetics of this sample is unknown. Keywords = commercial Keywords = dry active yeast Keywords: other
2005-08-01 | GSE1314 | GEO