Transcriptional Profiling of Cerebral Malaria
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE7814 | GEO | 2007/10/01
SECONDARY ACCESSION(S): PRJNA100039
REPOSITORIES: GEO
Similar Datasets
Project description:Cerebral malaria (CM) is a leading cause of death in the world. Better understanding of the pathogenesis of this disease is critical for the development of novel therapies. In this work, we investigated temporal gene expression profiles in the brains of CM-susceptible and CM-resistant mice during infection with P. Berghia ANKA (PbA). In this model of CM, susceptible mice develop neurological signs by day 6 post infection while resistant mice do not develop neurological manifestations during malarial infection. Experiment Overall Design: C57/B6 (CM-susceptible) and Balb/C (CM-resistant) mice were infected with PbA. Gene expression profiles from whole brains were obtained at day 0 (uninfected), day 1, day 3, and day 6.
2008-06-15 | E-GEOD-7814 | biostudies-arrayexpress
Project description:Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune adults, which results in great mortality and long-term sequelae. Recent reports based on histology of post-mortem brain tissue suggest that CM may be the common end point for a range of syndromes. Here, we have analysed the gene expression profiles in brain tissue taken from experimental CM (ECM)-susceptible, Plasmodium berghei ANKA (PbA)-infected C57BL/6 (B6) and CBA/CaH (CBA) mice with ECM. Gene expression profiles were largely heterogeneous between the two ECM-susceptible strains. These results, combined with experimental data, support the existence of distinct pathogenic pathways in CM. Keywords: disease state analysis
2007-10-11 | GSE6019 | GEO
Project description:Cerebral Malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. Currently, our understanding of the factors that trigger progression of malaria to CM is limited. Here, by infecting experimental CM (ECM) resistant (Balb/c) and ECM susceptible (C57BL/6) mice with ECM causing (ANKA) and non-ECM causing (NK65) Plasmodium berghei (Pb) parasite strains, we revealed that in resistant host, infection by ECM causing parasite develops similar to infection by non-ECM causing parasite in susceptible host in terms of parasite growth in host, disease course and host immune response against parasite. Our comparative gene expression analysis revealed that in Balb/c host, gene expression of Pb ANKA parasite is remarkably different from, the gene expression of Pb ANKA in C57BL/6 but similar to the gene expression of non-ECM causing Pb NK65 in C57BL/6. Thus, host has a critical influence on parasite behavior which ultimately determines the course of malaria disease.
2023-02-21 | GSE215359 | GEO
Project description:Gene expression patterns were investigated in well-defined genetically cerebral malaria-resistant (CM-R) and cerebral malaria-susceptible (CM-S) mouse strains. cDNA microarrays were used to search for differentially expressed genes in mouse brain. Four mouse strains, known to differ in susceptibility to cerebral malaria upon Plasmodium berghei ANKA infection, were compared: BALB/c and DBA/2 mice are CM-R, while C57BL/6 and CBA/J mice are CM-S.
2005-06-30 | E-MEXP-370 | biostudies-arrayexpress
Project description:We found that oral activated charcoal (oAC) provided significant protection against P. berghei ANKA-induced ECM, significantly increasing overall survival time compared to untreated mice. Protection from ECM by oAC was associated with a reduced numbers of splenic TNF+ CD4+ T cells and multifunctional IFNy+TNF+ CD4+ and CD8+ T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, a group of female C57BL/6 mice infected with PbA received Activated Charcoal. At day 6 p.i., and prior to the first deaths of untreated PbA-infected mice, 5 untreated PbA-infected mice (Group 1) and 5 AC-treated PbA-infected mice (Group 2) were killed and fresh blood (300-500�l per mouse) was collected and processed into RNA. Blood was also taken from uninfected control mice (�baseline�- Group 3).
2010-04-01 | E-MEXP-2594 | biostudies-arrayexpress
Project description:The development and outcome of cerebral malaria (CM) reflects a complex interplay between parasite-expressed virulence factors and host response to infection. To simultaneously analyze transcriptional programs in both parasite and host over the course of infection, we created microarrays to concurrently detect transcripts in the genomes of both Plasmodium berghei and mouse. Analysis of RNA from brain, lung, liver, and spleen of mice infected with P. berghei ANKA showed that parasite gene expression is readily detected in whole organ RNA. Comparison of CM-susceptible (C57BL/6) and CM-resistant (BALB/c) mice showed that both host and parasite display distinct organ-specific transcriptional signatures in susceptible versus resistant animals. Host genes whose expression differs between CM-resistant and CM-susceptible mice, at either baseline or induced by infection, tend to relate to humoral and immune response, complement activation, or cell-cell interactions, suggesting differences in immune function that may directly underlie protection from or susceptibility to CM. P. berghei, in contrast, displayed differential expression of genes related to apparent biosynthestic activities, with the majority of transcriptional activity observed in the lung. These data show that analysis of host and parasite gene expression profiles by hybridizing infected host samples to a single microarray is feasible, and can facilitate dissection of complex host-pathogen interactions. Keywords: Time course, Disease state analysis
2006-11-24 | GSE5672 | GEO
Project description:Cerebral Malaria (HCM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently the only treatment for HCM is the provision of anti-malarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify new potential adjunct treatments for HCM, we performed a non-biased whole brain transcriptomic time-course analysis of anti-malarial drug chemotherapy of murine experimental CM (ECM).
2018-07-03 | E-MTAB-6474 | biostudies-arrayexpress
Project description:Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R) and CM-susceptible (CM-S) mice, upon infection by Plasmodium berghei ANKA. We investigated mouse transcriptional responses prior to infection, and at early and late stages of infection by use of cDNA microarrays. Through a rigorous statistical approach with multiple testing corrections, we showed that P. berghei ANKA significantly altered brain gene expression in CM-R (BALB/c), and in CM-S (CBA/J and C57BL/6) mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation suggests that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In particular, we evidenced the down-regulation of genes involved in oxidative phosphorylation and the Reln pathway, and the up-regulation of genes involved in the NF-kB signalling pathway in CM-S mice. In addition, our data suggest that cerebral malaria and Alzheimers disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of beta-amyloid proteins in brains of CM-S mice, but not of CM-R mice. Our results indicate that microarray analyses can provide new insights into the key events that govern malaria pathogenesis.
2007-05-01 | E-MEXP-1018 | biostudies-arrayexpress
Project description:Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune adults, which results in great mortality and long-term sequelae. Recent reports based on histology of post-mortem brain tissue suggest that CM may be the common end point for a range of syndromes. Here, we have analysed the gene expression profiles in brain tissue taken from experimental CM (ECM)-susceptible, Plasmodium berghei ANKA (PbA)-infected C57BL/6 (B6) and CBA/CaH (CBA) mice with ECM. Gene expression profiles were largely heterogeneous between the two ECM-susceptible strains. These results, combined with experimental data, support the existence of distinct pathogenic pathways in CM. Experiment Overall Design: C57BL/6 and CBA/CaH mice were infected with 10e5 Plasmodium berghei ANKA-infected RBCs and monitored for ECM development. At onset of ECM symptoms, infected mice and naive controls were culled, perfused (in order to remove non-adherent circulating cells), and brains were removed. Total RNA was extracted from these brains and pooled (n=6 mice/ group). Pooled RNA samples were converted to cDNA and antisense cRNA, labelled and hybridized to GeneChip Mouse Genome 430 2.0 Arrays (Affymetrix, Surrey Hills, Australia). Arrays were scanned using the GeneChip Scanner 3000 (Affymetrix) and GeneChip Operating Software v1.1.1 (Affymetrix). Normalisation and initial analyses were carried out in GeneSpring v7 (Agilent Technologies). Values below 0.01 were set to 0.01. Each measurement was divided by the 50th percentile of all measurements in that sample. The data was filtered for genes flagged as present, which had at least an expression level of 50. Following this, a threshold of 2.5 fold up-regulation or down-regulation of genes differentially expressed during ECM was set.
2008-06-14 | E-GEOD-6019 | biostudies-arrayexpress
Project description:Infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) is a well-established experimental model of cerebral malaria (ECM). ECM is characterised by high levels of parasite sequestration and recruitment of pathogenic CD8+ T cells to the brain. The role of CD4+ T cells in this model has not yet been fully elucidated, although our laboratory has recently shown that CD4+ T cell depletion prior to infection results in significantly lower parasite burdens and protection from ECM. These data highlight a pathogenic role for CD4+ T cells in ECM. Our unpublished observations indicate that mice lacking the CD8+ T cell cytolytic effector molecule, Granzyme B, (GzmB), are resistant to ECM, showing markedly reduced parasite burdens. Late depletion of CD4+ T cells from PbA-infected GzmB-deficient mice results in enhanced parasite burdens, indicating that these cells may play an anti-parasitic role. In the present study, we have analysed splenic CD4+ T cell gene expression profiles in naïve C57BL/6 mice, and PbA-infected wild-type and GzmB-deficent mice to further our understanding of the CD4+ T cell response in ECM. Splenic CD4 T cells isolated by cell sorting from either uninfected C57BL/6 or PbA-infected C57BL/6 or B6.GzmB-/- mice at day 4 post-infection. Total RNA obtained from four mice per group.
2010-12-10 | E-GEOD-24903 | biostudies-arrayexpress