Differential gene expression profile of human neutrophils cultured with Plasmodium falciparum-parasitized erythrocytes
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PROVIDER: PRJNA464235 | ENA |
REPOSITORIES: ENA
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Project description:Neutrophils (PMNs) are the most abundant cellular component of our innate immune system, where they play central roles in the pathogenesis of and resistance to a broad range of diseases. However, their roles in malarial infection remain poorly understood. Therefore, we examined the transcriptional gene profile of human PMNs in response to Plasmodium falciparum-parasitized erythrocytes (iRBCs) by using oligonucleotide microarrays. Results revealed that PMNs induced a broad and vigorous set of changes in gene expression in response to malarial parasites, represented by 118 upregulated and 216 downregulated genes. The transcriptional response was characterized by the upregulation of numerous genes encoding multiple surface receptors, proteins involved in signal transduction pathways, and defense response proteins. This response included number of genes which are known to be involved in the pathogenesis of malaria and other inflammatory diseases. Gene enrichment analysis suggested that the biological pathways involved in the PMNs responses to the iRBCs included insulin receptor, Jak-STAT signaling pathway, mitogen activated protein kinase (MAPK), and interleukin and interferon-gamma signaling pathways. The current study provides fundamental knowledge on the molecular responses of neutrophils to malarial parasites, which may aid in the discovery of novel therapeutic interventions.
2018-05-07 | GSE114076 | GEO
Project description:Neutrophils (PMNs) are the most abundant cellular component of our innate immune system, where they play central roles in the pathogenesis of and resistance to a broad range of diseases. However, their roles in malarial infection remain poorly understood. Therefore, we examined the transcriptional gene profile of human PMNs in response to Plasmodium falciparum-parasitized erythrocytes (iRBCs) by using oligonucleotide microarrays. Results revealed that PMNs induced a broad and vigorous set of changes in gene expression in response to malarial parasites, represented by 118 upregulated and 216 downregulated genes. The transcriptional response was characterized by the upregulation of numerous genes encoding multiple surface receptors, proteins involved in signal transduction pathways, and defense response proteins. This response included a number of genes which are known to be involved in the pathogenesis of malaria and other inflammatory diseases. Gene enrichment analysis suggested that the biological pathways involved in the PMN responses to the iRBCs included insulin receptor, Jak-STAT signaling pathway, mitogen-activated protein kinase (MAPK), and interleukin and interferon-gamma (IFN-γ) signaling pathways. The current study provides fundamental knowledge on the molecular responses of neutrophils to malarial parasites, which may aid in the discovery of novel therapeutic interventions.
| S-EPMC6057315 | biostudies-literature
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:Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparum–infected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparum–modulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparum–infected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
2009-11-10 | GSE9861 | GEO
Project description:In order to identify an expression signature that might characterize the impact of Plasmodium parasites on NK cells, we have used Affymetrix oligonucleotide microarrays to examin the global gene expression profile of primary NK cells that have been co-incubated with P. falciparum infected red blood cells and have compared it to the expression pattern of NK genes induced by cytokine treatment.
2011-12-01 | GSE24791 | GEO
Project description:Neutrophils and erythrocytes are vital to the immune system and oxygen transport, respectively. However, the mechanisms by which hematopoietic niches support their development remain incompletely understood. In hematopoiesis research, zebrafish larvae are a common model for studying the development of definitive neutrophils and erythrocytes in the caudal hematopoietic tissue. In this study, we showed that erythrocytes predominantly reside inside the blood vessels of the CHT, while neutrophils stay outside. Ectopic vascular endothelium, induced by Bone Morphogenetic Protein 2b(Bmp2b) overexpression, attracts both cell types, with erythrocytes inside and neutrophils outside. CHT removal has minimal impact on definitive neutrophils from the ventral wall of the dorsal aorta (VDA) but severely affects definitive erythrocytes from the same source. Bulk RNA-sequencing identified epoa as a vital factor for erythrocyte generation within CHT endothelium. Overexpression of epoa through the lyve1b promoter, which is specifically expressed in vein, lymphatic vessels and CHT vein endothelial cells, rescued the erythrocyte reduction in epoa mutants. Our study reveals that the caudal hematopoietic tissue is differentially required for definitive erythrocytes and neutrophils.
2023-11-16 | GSE247730 | GEO
Project description:To study the effect of Plasmodium falciparum-infected erythrocytes on gene expression in NK92 cells, microarray analysis after 6, 12 and 24 hours of co-culture with either uRBC or iRBC was performed. The aim was to identify pathways in NK92 cells that are switched on after iRBC encounter in a time-dependent manner that will help to understand the mechanisms in innate immune defenses against Plasmodium falciparum infection.
2011-11-12 | GSE26876 | GEO
Project description:Background: Host iron deficiency is protective against severe malaria as the human malaria parasite Plasmodium falciparum depends on free iron from its host to proliferate. Due to the absence of transferrin, ferritin, ferroportin, and a functional heme oxygenase, the parasite’s essential pathways of iron acquisition, storage, export, and detoxification differ from those in humans and may thus be excellent targets for therapeutic development. However, the proteins involved in these processes in P. falciparum remain largely unknown. Experimental design: To identify iron-regulated mechanisms and putative iron transporters in the human malaria parasite Plasmodium falciparum 3D7, we carried out whole-transcriptome profiling using bulk RNA-sequencing. The parasites were cultured either using erythrocytes from a donors with high, medium (healthy) or low iron status (experiment 1); or with red blood cells from another healthy donor in the presence or absence of 0.7 µM hepcidin, a specific ferroportin inhibitor and iron-regulatory hormone (experiment 2). This concentration of hepcidin was reported to reduce binding of ferrous iron to ferroportin by 50% in vitro (39). Samples from three biological replicates each were harvested at the ring and trophozoite stage (6 – 9 and 26 – 29 hours post invasion, hpi) during the second intra-erythrocytic developmental cycle under the conditions specified.
2024-04-08 | E-MTAB-13411 | biostudies-arrayexpress
Project description:Sensitisation of endothelium to TNFalpha induced by cytoadherence of Plasmodium falciparum infected red blood cells
2007-06-05 | E-SGRP-3 | biostudies-arrayexpress
Project description:In order to identify an expression signature that might characterize the impact of Plasmodium parasites on NK cells, we have used Affymetrix oligonucleotide microarrays to examin the global gene expression profile of primary NK cells that have been co-incubated with P. falciparum infected red blood cells and have compared it to the expression pattern of NK genes induced by cytokine treatment. PBMCs were isolated from 3 healthy donors and were incubated with iRBCs, uRBCs, IL12 plus IL18 and without any stimulus. After 24 hours at 37ºC and 5%CO2, Natural killer cells were isolated by negative selection, checked for purity by flow cytometry and processed for RNA extraction and analysis with the Human Gene 1.0 Affymetrix array. The experiment was repeated 3 times (1-2 weeks apart) for each one of the 3 donors.
2011-12-01 | E-GEOD-24791 | biostudies-arrayexpress