The Parasite Intraerythrocytic Cycle and Human Circadian Cycle are Coupled During Malaria Infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium vivax Homo sapiens
PROVIDER: GSE209877 | GEO | 2023/06/12
REPOSITORIES: GEO
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Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197458 | GEO
Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197409 | GEO
Project description:The blood-stage infection of the malaria parasite, Plasmodium falciparum, exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, triggering 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes, or by a parasite-intrinsic oscillator. To distinguish between hypotheses, we examined the P. falciparum cycle in an in vitro culture system that lacks extrinsic cues from the host and show that P. falciparum has molecular signatures associated with circadian and cell-cycle oscillators. Each of four strains examined has a unique period, indicating strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator is responsible for Plasmodium’s rhythmic life cycle.
2019-12-10 | GSE141653 | GEO
Project description:To address whether T. brucei has a circadian clock we probed its transcriptome by RNA-seq, searching for transcripts oscillating with a 24 hr period. For this we entrained/ synchronized parasites in vitro for three days using temperature and light as environmental stimuli and then collected parasite RNA every four hours for two consecutive days. Parasite RNA was subjected to RNA-seq analysis. We performed this protocol on two stages of the T. brucei life cycle (bloodstream and insect procyclic forms).
2017-02-10 | E-MTAB-4952 | biostudies-arrayexpress
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2020-07-17 | GSE145855 | GEO
Project description:The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Despite comprising up to 5% of the parasite genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due antigenic variation. In this model, pir genes are called cirs and may be involved in this mechanism allowing evasion of host immune responses. We have annotated the cir repertoire and performed detailed bioinformatic characterization of the encoded CIR proteins. Two major sub-families were identified: A and B, which display different amino acid motifs, and are thus predicted to have undergone functional divergence. The expression of all cirs was analyzed via RNA sequencing and microarray. Up to 40% of cir genes were expressed in the parasite population during infection, including members of both sub-families. Dominant cir transcripts could also be identified. Finally, specific cir genes were expressed at different time points during the blood stages of infection. Together our data characterizing the cir genes and their expression throughout the intra-erythrocytic cycle of development indicate that CIR proteins are likely to be important for parasite survival in the host. P. chabaudi AS is a highly synchronous parasite for which development in the blood follows its hostM-bM-^@M-^Ys circadian rhythm. Twelve time-points were then collected; one every two hours, to cover the entire 24 h cycle of blood stage development. At the peak of parasitaemia, one mouse was sacrificed at each time point and thin blood films were made and stained with Giemsa for optical microscopy. The pan-rodent microarray was designed using the OligoRankPick program as previously described: Liew, K et al.2010, Defining species specific genome differences in malaria parasites. BMC genomics 11,128. The RNA preparation, Cy-dye coupling to cDNA, hybridization and slide scanning were performed as described by Bozdech and colleagues Bozdech, Z et al 2003, The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol 1, E5.
2012-05-31 | E-GEOD-33333 | biostudies-arrayexpress
Project description:Trypanosoma vivax is a major pathogen of domestic cattle and wildlife across sub-Saharan Africa. For many years, the WTSI has had a research interest in developing a genome sequence for T. vivax, as part of a wider programme concerning African trypanosome parasites of Humans and animals. In 2012 a draft genome sequence for T. vivax Y486 was published by the WTSI and our collaborators in comparison with related species, T. brucei and T. congolense. This study identified numerous putative genes in T. vivax that have no known affinity and are therefore species-specific. A related transcriptomic study confirmed that some of these putative genes are transcribed, but lacked accuracy and was based on a single parasite life stage only. Until recently, it has not been possible to culture different T. vivax life stages in refined media. There is now the opportunity to use new approaches to produce whole cell RNA for both insect and bloodstream parasite stages. We sequence stage-specific cDNA and identify stage-specific genes, and compare these features with similar data already available for T. brucei and T. congolense, which display substantial differences in their developmental cycles. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2013-03-07 | E-ERAD-100 | biostudies-arrayexpress
Project description:It is well known that host-microbes and immunity interactions are influenced by dietary patterns, as well as daily environmental light-dark (LD) cycles that entrain circadian rhythms in the host. Emerging data has highlighted the importance of diet patterns and timing on the interaction among circadian rhythms, gut microbiome, and immunity, however, their impacts on LD cycles are less reported. Therefore, we aim to study how LD cycles regulate the homeostatic crosstalk between gut microbiome, hypothalamic and hepatic circadian clock oscillations and immunity. We hypothesized that different environmental LD cycles: (1) constant darkness, LD0/24; (2) short light, LD8/16; (3) normal LD cycle, LD12/12; (4) long light, LD16/8; and (5) constant light, LD24/0, may affect immunity and metabolism to varying degrees. Therefore, 240 mice were managed with chow diets (CD) and antibiotics treatments (ABX) under five different LD cycles for 42 days. The colonic (co) and cecum (ce) contents were obtained for studying their impacts on gut microbiome using 16S rRNA sequencing.
2023-03-10 | GSE226852 | GEO
Project description:The parasitic flagellate Trypanosoma vivax is a cause of animal trypanosomiasis across Africa and South America. The parasite has a digenetic life cycle, passing between mammalian hosts and insect vectors, and a series of developmental forms adapted to each life cycle stage. Transcriptomic and proteomic studies of the related parasites T. brucei and T. congolense have shown how gene expression is regulated during their development. New methods for in vitro culture of the T. vivax insect stages have allowed us to describe global gene expression throughout the complete T. vivax life cycle for the first time. We combined transcriptomic and proteomic analysis of each life stage using RNA-seq and mass spectrometry respectively, to identify genes with patterns of preferential transcription or expression. While T. vivax is similar to related species in several ways, (e.g. developmental regulation of energy metabolism, restricted expression of a dominant variant antigen, and expression of ‘Fam50’ proteins in the insect mouthparts), we identify significant differences in gene expression affecting metabolism in the fly and a suite of T. vivax-specific genes with predicted cell-surface expression that are preferentially expressed in the mammal (‘Fam29, 30’) or the vector (‘Fam34, 35, 43’). Thus, T. vivax differs significantly from other African trypanosomes in the developmentally-regulated proteins it expresses on its cell surface and thus, in the structure of the host-parasite interface. These unique features may yet explain the species differences in life cycle and could, in the shape of bloodstream-stage proteins that do not undergo antigenic variation, provide targets for therapy.
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Project description:It is well known that host-microbes and immunity interactions are influenced by dietary patterns, as well as daily environmental light-dark (LD) cycles that entrain circadian rhythms in the host. Emerging data has highlighted the importance of diet patterns and timing on the interaction among circadian rhythms, gut microbiome, and immunity, however, their impacts on LD cycles are less reported. Therefore, we aim to study how LD cycles regulate the homeostatic crosstalk between gut microbiome, hypothalamic and hepatic circadian clock oscillations and immunity. We hypothesized that different environmental LD cycles: (1) constant darkness, LD0/24; (2) short light, LD8/16; (3) normal LD cycle, LD12/12; (4) long light, LD16/8; and (5) constant light, LD24/0, may affect immunity and metabolism to varying degrees. Therefore, 240 mice were managed with chow diets (CD) and antibiotics treatments (ABX) under five different LD cycles for 42 days. The liver (LIV), hypothalamus (HYP), inguinal white adipose tissue (iWAT), ileum epithelium (ILE), colon epithelium (COL), jejunum epithelium (JEJ), cecum epithelium (CEC), spleen (SPL), mammary gland (MAG), and thymus gland (THY) tissues were obtained for studying their impacts immunity using RNA-Seq data.
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