Metabolite profile of mice hippocampus following Toxoplasma gondii infection
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ABSTRACT:
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase
SUBMITTER: Junjun He
PROVIDER: MTBLS1890 | MetaboLights | 2021-01-27
REPOSITORIES: MetaboLights
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Project description:<p><strong>BACKGROUND:</strong> The protozoan parasite Toxoplasma gondii infects and alters the neurotransmission in cerebral cortex and other brain regions, leading to neurobehavioral and neuropathologic changes in humans and animals. However, the molecules that contribute to these changes remain largely unknown.</p><p><strong>METHODS:</strong> We have investigated the impact of T. gondii infection on the overall metabolism of mouse cerebral cortex. Mass-spectrometry-based metabolomics and multivariate statistical analysis were employed to discover metabolomic signatures that discriminate between cerebral cortex of T. gondii-infected and uninfected control mice.</p><p><strong>RESULTS:</strong> Our results identified 73, 67 and 276 differentially abundant metabolites, which were involved in 25, 37 and 64 pathways at 7, 14 and 21 days post-infection (dpi), respectively. Metabolites in the unsaturated fatty acid biosynthesis pathway were upregulated as the infection progressed, indicating that T. gondii induces the biosynthesis of unsaturated fatty acids to promote its own growth and survival. Some of the downregulated metabolites were related to pathways, such as steroid hormone biosynthesis and arachidonic acid metabolism. Nine metabolites were identified as T. gondii responsive metabolites, namely galactosylsphingosine, arachidonic acid, LysoSM(d18:1), L-palmitoylcarnitine, calcitetrol, 27-Deoxy-5b-cyprinol, L-homophenylalanine, oleic acid and ceramide (d18:1/16:0).</p><p><strong>CONCLUSIONS:</strong> Our data provide novel insight into the dysregulation of the metabolism of the mouse cerebral cortex during T. gondii infection and have important implications for studies of T. gondii pathogenesis.</p>
2020-04-23 | MTBLS770 | MetaboLights
Project description:Toxoplasma gondii is a protozoan parasite with a remarkable neurotropic affinity. We recently showed that T. gondii infection can alter the global metabolism of the cerebral cortex of the mice. However, the impact of this infection on the metabolism of the cerebellum remained unclear. In this study, we compared the metabolomic profiles of mouse cerebellum following acute and chronic infection with T. gondii. Three-week-old female BALB/c mice (n = 36) were commercially obtained from Lanzhou University Laboratory Animal Center (Lanzhou, China). Mice were separated into 6 groups (6 mice/group). The mice in the infected groups were challenged with 10 T. gondii cysts of PRU strain suspended in 0.5 ml phosphate-buffered saline (PBS), whereas the mice in the control groups were sham treated with 0.5 ml PBS only. All mice were provided non-medicated feed and water ad libitum during the experiment. The mice were monitored twice daily for signs of illness and mortality. At 7, 14, and 21 days post infection (dpi), mice from infected and control group were humanely sacrificed by CO2 asphyxiation and cerebellum of each mouse was dissected with scissors and forceps. Then, the metabolite profile changes in the cerebellum of mice following infection of T. gondii was analyzed.
2020-04-27 | MTBLS1537 | MetaboLights
Project description:Differentiation mutants in the protozoan parasite Toxoplasma gondii.
| PRJNA92953 | ENA
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.
2009-09-17 | GSE18085 | 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 ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken. Chicken embryonic fibroblasts were cultivated in vitro and infected with different strains of Toxoplasma gondii; host transcriptional responses were then analyzed at 24 hours post-infection.
2011-05-27 | E-GEOD-29563 | biostudies-arrayexpress
Project description:Toxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken. Chicken embryonic fibroblasts were cultivated in vitro and infected with different strains of Toxoplasma gondii (Type II = ME49, Type III = CEP); host transcriptional responses were then analyzed at 24 hours post-infection.
2011-05-27 | E-GEOD-29562 | biostudies-arrayexpress
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:Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which can
infect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studies
have estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of these
people will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limiting
flu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,
particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. In
immunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptional
response of macrophages to T gondii infection.
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
| EGAS00001001708 | EGA
Project description:Toxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken.
2011-05-27 | GSE29563 | GEO