Transcriptomics of Toxoplasma gondii enteroepithelial stages
Ontology highlight
ABSTRACT:
ORGANISM(S): Toxoplasma gondii
PROVIDER: GSE108740 | GEO | 2018/03/30
REPOSITORIES: GEO
Similar Datasets
Project description:Toxoplasma gondii is an apicomplexan parasite that approximately infects one third of the human population worldwide. When sporulated oocysts that are shed in the faeces of infected felids are accidentally ingested through contaminated food or water, sporozoites can infect the intestine of the intermediate host. Upon this infection, the fast replicating tachyzoites then disseminate overall the body and can cross the blood-brain, blood-retina or the blood-placenta barrier. Eventually, immune pressure will lead to differentiation into the slow replicating bradyzoites that are contained within tissue cysts for life. Despite the importance of sporulation for transmission, the process is not yet understood. We therefore exploited Illumina Next-Generation RNA-Sequencing to analyse the transcriptome of oocysts in the process of sporulation and compared it to unsporulated and sporulated oocysts. We thus identified genes that are highly specific to the sporulation process and that may be involved in the formation of sporozoites.
2022-06-20 | GSE206344 | GEO
Project description:The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. These data characterize bradyzoites and tachyzoites treated with NaFAc.
2022-01-07 | ST002053 | MetabolomicsWorkbench
Project description:Sexual reproduction of Toxoplasma gondii, which is restricted to the small intestine of felids, is sparsely documented in studies involving domestic cats, which also raises ethical concerns. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. AP2XI-2 and AP2XII-1 likely synergize to suppress gene expression in tachyzoites, but their modus operandi is still enigmatic. We therefore characterized their interactomes.
2023-09-16 | PXD042658 | Pride
Project description:Sexual reproduction of Toxoplasma gondii, which is restricted to the small intestine of felids, is sparsely documented in studies involving domestic cats, which also raises ethical concerns. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites, as revealed by mass spectrometry-based proteomic analyses of the parasites.
2023-09-16 | PXD039400 | Pride
Project description:Toxoplasma gondii is an obligate intracellular parasite which can cause toxoplasmosis. Surface and secreted proteins of T. gondii play important roles in infection and immunity, and also are antigen targets in immunological diagnosis and vaccine development. However, it is difficult to investigate identities and antigenicities of surface and secreted proteins due to limitation of surface protein extraction methods. In this study, a total of 785 potential surface and secreted proteins of T. gondii RH tachyzoites were identified using a method combination of biotin labeling, avidin chromatography isolation, and high flux proteomics (LC-MS/MS). Among the highly-expressed 65 proteins, 43 proteins (66%) were originally annotated as surface or secreted proteins in the released T. gondii genomes, which proved the method combination to be a credible strategy. Furthermore, the transcriptomic responses and cytokine secretions induced by the isolated proteins, the live T. gondii RH tachyzoites infection, and the live pathogenic E. coli infection, in the human peripheral blood monocyte THP-1 cell lines, were comparatively analyzed to reveal antigenicities and immunobiological properties of T. gondii surface and secreted proteins. The transciptomic profiles induced by the isolated proteins were similar to those induced by the live bacterium infection, but were different from those induced by the live parasite infection. Contrary to the low cytokine secretion induced by the live parasite infection, the isolated proteins induced significant cytokine and chemokines secretion. Especially, the secretions of several chemokines induced by the isolated proteins were even higher than those induced by the live bacterium infection. These data suggested that T. gondii surface and secreted proteins were effective antigens, while the live parasite could evade the host innate immunity. This study comprehensively revealed the identities and antigenicities of T. gondii surface and secreted proteins, which laid foundation for further screening new T. gondii antigens, developing immunological diagnosis methods, and studying host immune response to T. gondii infection.
2017-09-20 | GSE103985 | GEO
Project description:Cyst formation is a key feature of the T. gondii life cycle but the genetic networks that drive this process are not yet fully characterized. To identify new components of this network, we compared T. gondii to its nearest extant relative Hammondia hammondi given the critical differences between these species in the timing and efficiency of cyst formation. Using transcriptional data from critical developmental and pH exposure time points from both species, we identified the gene TGVEG_311100, which we named Regulator of Cystogenesis 1 (ROCY1), as being both necessary and sufficient for cyst formation in T. gondii. Compared to WT parasites, TGVEG?ROCY1 parasites formed significantly fewer tissue cysts in response to alkaline pH stress in vitro and cysts were nearly undetectable in mouse brains for up to 9 weeks post-infection. Overexpression of tagged ROCY1 in WT parasites was sufficient to induce cyst formation in vitro in both WT and ROCY1-deficient parasites, demonstrating that ROCY1 is both necessary and sufficient for cyst formation. Moreover this induction of cyst formation required at least 1 of 3 predicted CCCH Zinc finger domains. Mice chronically infected with ?ROCY1 parasites had detectable tachyzoites in the brain for up to 37 days post-infection (while mice infected with WT parasites did not), and CNS transcriptional analyses at day 30 post-infection throughout the chronic phase of infection revealed inflammatory signatures consistent with acute infection in ?ROCY1 parasites compared to WT. Despite our inability to detect brain cysts in infected mice, both WT and ?ROCY1 knockout parasites reactivated after dexamethasone treatment with similar timing and magnitude for up to 5 months post infection, challenging the paradigm that long term parasite persistence in the CNS requires cyst formation. These data identify a new regulator of cyst formation in T. gondii that is both necessary and sufficient for cyst formation, and whose function relies on its conserved nucleic acid binding motif.
2023-08-11 | GSE211957 | GEO
Project description:The innate immune response of mucosal epithelial cells during pathogen invasion plays a central role in immune regulation in the gut. Toxoplasma gondii (T. gondii) is a protozoan intracellular parasite that is usually transmitted through oral infection. Although much of the information on immunity to T. gondii has come from intra-peritoneal infection models, more recent studies have revealed the importance of studying immunity following infection through the natural per-oral route. Oral infection studies have identified many of the key players in the intestinal response; however, they have relied on responses detected days to weeks following infection. Much less is known about how the gut epithelial layer senses and reacts during initial contact with the pathogen. Given the importance of epithelial cells during pathogen invasion, this study uses an in vitro approach to isolate the key players and examine the early response of intestinal epithelial cells during infection by T. gondii. We show that human intestinal epithelial cells infected with T. gondii elicit rapid MAPK phosphorylation, NF-κB nuclear translocation, and secretion of interleukin (IL)-8. Both ERK1/2 activation and IL-8 secretion responses were shown to be MyD88 dependent and TLR2 was identified to be involved in the recognition of the parasite regardless of the parasite genotype. Furthermore, we were able to identify additional T. gondii-regulated genes in the infected cells using a pathway-focused array. Together, our findings suggest that intestinal epithelial cells were able to recognize T. gondii during infection, and the outcome is important for modulating intestinal immune responses. Oral infection studies have demonstrated an increase in several cytokines and chemokines in response to T.gondii infection; however, the mixed population of the intestinal mucosa did not allow for the determination of the relative role that specific cell populations play in the production of these mediators. To address the role of intestinal epithelial cells to modulate the cytokine environment early following infection, we used specific pathway arrays to identify cytokines and chemokines induced 4 hours after exposure to T. gondii. At this time point most cells have become infected, but the parasites have not replicated.
2010-05-05 | E-GEOD-18085 | biostudies-arrayexpress
Project description:Toxoplasma gondii is a eukaryotic parasite that form latent cyst in the brain of immunocompetent individuals. The latent parasites infection of the immune privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons long-term infection are unknown.. It has long been known that T. gondii specifically differentiate into a latent form (bradyzoite) in neurons, but how the infected neuron is responding to the infection remain to be elucidated. We have established a new in vitro model resulting in the production of fully mature bradyzoites cysts in brain cells. Using dual, host and parasite, RNA-seq we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse. The establishment of this new in vitro model allows to investigate both the dynamics of the parasite differentiation and the specific response of neurons to the long term infection by this parasite.
2021-09-23 | GSE168465 | GEO
Project description:The protozoan parasite Toxoplasma gondii causes serious opportunistic disease due to its ability to persist in patients as latent tissue cysts. The molecular mechanisms coordinating conversion between proliferative parasites (tachyzoites) and latent cysts (bradyzoites) are not fully understood. We previously showed that phosphorylation of eIF2α accompanies bradyzoite formation, suggesting that this clinically relevant process involves regulation of mRNA translation. In this study, we investigated the composition and role of eIF4F multi-subunit complexes in translational control. Using CLIPseq, we find that the cap-binding subunit, eIF4E1, localizes to the 5’-end of all tachyzoite mRNAs, many of which show evidence of stemming from heterogenous transcriptional start sites. We further show that eIF4E1 operates as the predominant cap-binding protein in two distinct eIF4F complexes. Using genetic and pharmacological approaches, we found that eIF4E1 deficiency triggers efficient spontaneous formation of bradyzoites without stress induction. Consistent with this result, we also show that stress-induced bradyzoites exhibit reduced eIF4E1 expression. Overall, our findings establish a novel role for eIF4F in translational control required for parasite latency and microbial persistence.
2024-03-26 | GSE262241 | GEO
Project description:MOB1 is a conserved protein that regulates cellular proliferation versus apoptosis, centrosome duplication and cellular differentiation in multicellular eukaryotes and also cytokinesis and division axis orientation in unicellular and multicellular eukaryotes. Toxoplasma gondii, an obligate intracellular parasite of veterinary and medical importance, presents one MOB1 protein. T. gondii interconverts between several cellular stages during its life cycle, namely between fast replicating tachyzoite and slow replicating bradyzoite stages during its asexual cycle, a key ability for its success as a parasite. Bradyzoites produce tissue cysts, establishing a chronic infection that enables recrudescence. Conversion is dependent on cell cycle regulation and involves cell differentiation and regulation of replication. This led us to select MOB1 as a strong candidate to be involved in the Toxoplasma replication process. To elucidate how MOB1 acts in T. gondii, we employed a proximity biotinylation method and identified the MOB1 interactome. Toxoplasma gondii RH tachyzoites were transfected with BirA containing plasmid vectors for random integration and two strains were isolated. The control strain expresses a FLAG-BirA recombinant protein while the test strain expresses a FLAG-BirA-MOB1 recombinant protein. Biotinylated proteins were purified using streptavidin-agarose beads. The purified proteins were trypsinized and analyzed by nanoLC-MS/MS.
2022-02-16 | PXD028781 | Pride