Mus musculus
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ABSTRACT:
PROVIDER: PRJNA97825 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Analysis of transcriptional response to Plasmodium berghei ANKA infection in cerebral malaria susceptible C57BL/6 mouse brains as well as cerebral malaria resistant BXH2 mice which carry a severe hypomorphic Irf8-R294C allele. Interferon Regulatory Factor 8 (IRF8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. BXH2 mice harbor a loss-of-function allele at Irf8 (Irf8-R294C) that causes susceptibility to infection with intracellular pathogens, including Mycobacterium tuberculosis. We report that XH2 are completely resistant to the development of cerebral malaria following Plasmodium berghei ANKA infection. Comparative transcriptional profiling of brain RNA as well as chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) was used to identify IRF8-regulated genes whose expression is associated with pathological acute neuroinflammation. Genes up-regulated by infection were strongly enriched for IRF8 binding sites, suggesting that IRF8 acts as a transcriptional activator in inflammatory programs. These lists were enriched for myeloid-specific pathways, including interferon responses, antigen presentation and Th1 polarizing cytokines. We show that inactivation of several of these downstream target genes confers protection against experimental cerebral malaria. We also report strong overlap between genes bound and regulated by IRF8 during cerebral malaria and genes regulated in the lungs of M. tuberculosis infected mice. This IRF8-dependent network contains several genes recently identified as risk factors in acute and chronic human inflammatory conditions. In summary, this work defines a common core of IRF8-bound genes forming a critical inflammatory host-response network. Comparison of whole brain transcript profiles for wildype C57BL/6 mice versus severely hypomorphic Irf8-R294C BXH2 mice following experimental infection with Plasmodium berghei ANKA (d7). Baseline (d0) profiles are also compared. Pleaes note that each sample record represents 2-4 replicates and sample data table contains mean, standard error of the mean (SEM), and quality for the replicates. The non_normalized data matrix contains raw data for each replicate (total 12 samples).
2015-01-16 | E-GEOD-65036 | 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:Plasmodium berghei ANKA infection in mice is used as a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. The response of brain cells such as microglia has been little investigated, and may play a role in the pathogenesis or regulation of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1 Interferon signaling is important for activation. This dataset contains the transcriptome of brain microglia of infected mice in the presence and absence of Type I interferon signaling, with the aim of identifying the genes involved in this pathway in microglia during experimental cerebral malaria. Refererence: Capuccini et al 2016, Scientific Reports, 6:39258 The global gene expression profiles from RNA of microglia isolated from uninfected and P berghei-infected wild-type C57BL/6 mice and and IFNA Receptor Knock-out mice using Illumina Beadarrays.
2018-09-07 | GSE119650 | GEO
Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection. There is evidence that repeated parasite exposure promotes resistance against CM, as indicated by the low incidence of CM in adults in malaria-endemic regions. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, a microarray study done utilising the tractable Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth infection.
2019-02-19 | E-MTAB-5513 | biostudies-arrayexpress
Project description:Analysis of transcriptional response to Plasmodium berghei ANKA infection in cerebral malaria susceptible C57BL/6 mouse brains as well as cerebral malaria resistant BXH2 mice which carry a severe hypomorphic Irf8-R294C allele. Interferon Regulatory Factor 8 (IRF8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. BXH2 mice harbor a loss-of-function allele at Irf8 (Irf8-R294C) that causes susceptibility to infection with intracellular pathogens, including Mycobacterium tuberculosis. We report that XH2 are completely resistant to the development of cerebral malaria following Plasmodium berghei ANKA infection. Comparative transcriptional profiling of brain RNA as well as chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) was used to identify IRF8-regulated genes whose expression is associated with pathological acute neuroinflammation. Genes up-regulated by infection were strongly enriched for IRF8 binding sites, suggesting that IRF8 acts as a transcriptional activator in inflammatory programs. These lists were enriched for myeloid-specific pathways, including interferon responses, antigen presentation and Th1 polarizing cytokines. We show that inactivation of several of these downstream target genes confers protection against experimental cerebral malaria. We also report strong overlap between genes bound and regulated by IRF8 during cerebral malaria and genes regulated in the lungs of M. tuberculosis infected mice. This IRF8-dependent network contains several genes recently identified as risk factors in acute and chronic human inflammatory conditions. In summary, this work defines a common core of IRF8-bound genes forming a critical inflammatory host-response network.
2015-01-16 | GSE65036 | 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: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:Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the contribution of microglia, the brain resident macrophages, to this severe complication. We have examined the responses of microglia in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Genome wide transcriptomic analysis of these cells revealed that thousands of transcripts were differentially expressed at two different time points during the infection. The analysis indicated that proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Together, our data offer a unique insight into the responses of microglia in the brain during ECM.
2016-12-19 | GSE86082 | GEO
Project description:Measure the effect of TCRβ expression on the transcriptional profile of CD11bhighCD14+F4/80+ macrophages sorted from mouse spleen on day 6 post-infection with Plasmodium berghei ANKA malaria
2018-03-09 | GSE111593 | GEO