Differential gene expression analysis of murine liver and kidney following exposure to malarial parasite
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31686 | GEO | 2012/08/01
SECONDARY ACCESSION(S): PRJNA145651
REPOSITORIES: GEO
Similar Datasets
Project description:Global changes in murine liver and kidney transcriptome were analyzed following different levels of malarial parasite infection.Known levels of parasites were injected in mice and transcriptomic changes were recorded with comparison to control non infected healthy mice. Two color ,Organism: Mus Musculus, Genotypic Technology designed "Custom Agilent Mus Musculus 8x15k GE Microarray (AMADID-016270) "
2012-07-31 | E-GEOD-31686 | biostudies-arrayexpress
Project description:Induction of parasite-specific CD4+ Th1 cell responses is a promising strategy for designing effective blood-stage malaria vaccines; however, the underlying regulatory mechanisms remain largely unknown. This study demonstrated that ATG5 deficiency in myeloid cells can significantly inhibit the growth of rodent blood-stage malarial parasites by enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency promoted myeloid cell (Ly6G-CD11b+F4/80-) survival and subsequently increased MCP-1 production in parasite-infected mice. Ly6G-CD11b+F4/80- cell-derived MCP-1 interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2/STAT4 pathway. Notably, recombinant MCP-1 significantly improved parasite-specific CD4+ Th1 responses of the whole-killed blood-stage vaccine. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cell survival via MCP-1 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of effective antimalarial vaccines.
2023-12-16 | GSE239405 | GEO
Project description:During infections with malaria parasites P. vivax, patients exhibit rhythmic fevers every 48 hours. These fever cycles correspond with the time parasites take to traverse the Intraerythrocytic Cycle (IEC) and may be guided by a parasite-intrinsic clock. Different species of Plasmodia have cycle times that are multiples of 24 hours, suggesting they may be coordinated with the host circadian clock. We utilized an ex vivo culture of whole blood from patients infected with P. vivax to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC were correlated across multiple patients, suggesting that the cycles are coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable anti-malarial therapies that disrupt this coupling.
2023-06-12 | GSE209877 | GEO
Project description:The ability to respond to stressful host environments is crucial for the survival of intracellular pathogens, during which transporters play key roles in the nutrient scavenging, such as lipid uptake. Here we discover a conserved malarial gene that orchestrates the parasitic adaption in the terminally differentiated, phospholipid scarce erythrocytes. The expression level of this gene, here named CAP, is the intensively upregulated in the erythrocyte-infecting parasites than the reticulocyte-infecting counterparts. We show that CAP encodes a small protein exported onto the membrane of infected erythrocytes where it interacts with host CTL1, a choline and ethanolamine transporter, and upregulates biosynthesis of phosphatidylcholine and phosphatidylethanolamine, the major component of parasite membrane. Deletion of CAP causes Plasmodium to upturn reticulocyte invasion and sexual stage differentiation. This work presents a novel mechanism for intracellular parasite to import lipid precursors into parasitized cells by manipulating an endogenous host transporter.
2024-01-12 | GSE252704 | GEO
Project description:P. falciparum is the deadliest causative agent of human malaria. This parasite has historically developed resistance to many drugs, including the current frontline treatments, so new therapeutic targets are needed Our previous work on guanine quadruplexes (G4s) in the parasite’s DNA and RNA has highlighted their influence on parasite biology, and also revealed G4 stabilising compounds as promising candidates for drug repositioning. In particular, quarfloxin, a former anticancer agent, kills blood-stage parasites at all developmental stages, with fast rates of kill and nanomolar potency. Here we explored the molecular mechanism of quarfloxin and its related derivative CX-5461. In vitro, both compounds bound to P. falciparum-encoded G4 sequences. In cellulo, quarfloxin was more potent than CX-5461, and could prevent establishment of blood-stage malaria in vivo in a murine model. CX-5461 showed clear DNA damaging activity, as reported in human cells, while quarfloxin caused weaker signatures of DNA damage. Both compounds caused transcriptional dysregulation in the parasite, but the affected genes were largely different, again suggesting different modes of action. Therefore, CX-5461 may act primarily as a DNA damaging agent in both Plasmodium parasites and mammalian cells, whereas the complete anti-malarial mode of action of quarfloxin may be parasite-specific, and remains elusive.
2024-01-02 | GSE235142 | GEO
Project description:Toxoplasma gondii is an obligate intracellular protozoan parasite which, upon invasion of host cells, injects virulence factors that are known to induce dramatic alterations in host cell signaling. Although much work has been directed at understanding the impact of specific secreted proteins on host cell function, dissecting the host response to injected virulence factors has been complicated by the fact that injection is rapidly followed by invasion, establishment of a parasitophorous vacuole in the host cell cytoplasm, secretion of parasite proteins from other specialized organelles, and remodeling of the host cell cytoskeleton Here, we describe the global macrophage transcriptional response to secreted proteins and show that injection of rhoptry contents alone is sufficient to trigger a dramatic host cells response. We further define modules of genes that are regulated in a parasite strain-specific manner by activation of the host transcription factor, STAT6. Our approach leverages transgenic parasites that express mCherry and inject Cre-recombinase along with normal virulence factors into the cytoplasm of host cells. Primary macrophages were recovered from transgenic reporter mice (Ai6) that express the ZsGreen1 fluorochrome when exposed to cre recombinase, allowing for the identification of a unique population of cells into which T. gondii injects virulence factors but does not infect (uninfected-injected, or U-I). Transcriptional profiling of these U-I cells compared to infected cells or uninfected controls from the same cultures was carried out, using bone marrow derived macrophages (BMDM) from either WT or STAT6-/- mice. This data allows us to interrogate the outcomes T. gondii induced STAT signaling in both infected and U-I cell populations, and to resolve effects of injected virulence factors, like ROP16, from those changes induced by infection.
2019-03-01 | GSE55892 | GEO
Project description:The aim was to understand the molecular basis of the parasite response to DR. Transcriptomic analysis of synchronized wildtype parasites, collected with 4h intervals, from mice under the two dietary conditions. We found that WT parasites on DR and control diets have different transcriptomes, with a remarkable general repression of transcription in DR.
2017-07-14 | GSE69628 | GEO
Project description:Intracellular microbes have evolved efficient strategies for transitioning from one cell to another in a process termed intercellular transmission. Here we show that host cell transmission of the obligate intracellular parasite Toxoplasma gondii is closely tied to specific cell cycle distributions, with egress and reinvasion occurring most proficiently by parasites in the G1 phase. We also reveal that Toxoplasma undergoes marked changes in mRNA expression when transitioning from the extracellular environment to its intracellular niche. These mRNA level changes reflect a modal switch from expression of proteins involved in invasion, motility and signal transduction in extracellular parasites to expression of metabolic and DNA replication proteins in intracellular parasites. Host cell binding and signalling associated with the discharge of parasite secretory proteins was not sufficient to induce this switch in gene expression, suggesting that the regulatory mechanisms responsible are tied to the establishment of the intracellular environment. The genes whose expression increased after parasite invasion belong to a progressive cascade known to underlie the parasite division cycle indicating that the unique relationship between the G1 phase and invasion effectively synchronizes short-term population growth. This work provides new insight into how this highly successful parasite competently transits from cell to cell. Three sample types were harvested: extracellular, intracellular 0hr, intracellular 2hr. 2 replicates each. Expression for >80% of the regulated genes exhibits a steady downregulation during invasion.
2010-12-27 | E-GEOD-20480 | biostudies-arrayexpress
Project description:Intracellular microbes have evolved efficient strategies for transitioning from one cell to another in a process termed intercellular transmission. Here we show that host cell transmission of the obligate intracellular parasite Toxoplasma gondii is closely tied to specific cell cycle distributions, with egress and reinvasion occurring most proficiently by parasites in the G1 phase. We also reveal that Toxoplasma undergoes marked changes in mRNA expression when transitioning from the extracellular environment to its intracellular niche. These mRNA level changes reflect a modal switch from expression of proteins involved in invasion, motility and signal transduction in extracellular parasites to expression of metabolic and DNA replication proteins in intracellular parasites. Host cell binding and signalling associated with the discharge of parasite secretory proteins was not sufficient to induce this switch in gene expression, suggesting that the regulatory mechanisms responsible are tied to the establishment of the intracellular environment. The genes whose expression increased after parasite invasion belong to a progressive cascade known to underlie the parasite division cycle indicating that the unique relationship between the G1 phase and invasion effectively synchronizes short-term population growth. This work provides new insight into how this highly successful parasite competently transits from cell to cell.
2010-12-27 | GSE20480 | GEO
Project description:Trichinellosis of human and other mammals was caused through the ingestion of the parasite，Trichinella spiralis，contaminated meat. It is a typical zoonotic disease that affects more than 10 million people world-wide. Parasites of Trichinella genus are unique intracellular pathogens. Adult Trichinella parasites directly release newborn larvae which invade striated muscle cells and causes diseases. In this study, we profiled the global transcriptome in the three developmental stages of T. spiralis. The transcriptomic analysis revealed the global gene expression patterns from newborn larval stage through muscle larval stage to adults. Thousands of genes with stage-specific transcriptional patterns were described and novel genes involving host-parasite interaction were identified. More than 45% of the protein-coding genes showed evidence of transcription from both sense and antisense strands which suggests the importance of RNA-mediated gene regulation in the parasite. This study presents a first deep analysis of the transcriptome of T. spiralis, providing insight information of the parasite biology.
2013-06-18 | GSE39151 | GEO