Toxoplasma gondii infection can regulate the expression of tumour necorsis factor-alpha receptors on human cell in vitro

2002 ◽  
Vol 24 (5) ◽  
pp. 271-279 ◽  
Author(s):  
Dorra Derouich-Guergour ◽  
Delphine Aldebert ◽  
Ines Vigan ◽  
Evelyne Jouvin-Marche ◽  
Patrice N. Marche ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Human Cell ◽  
Alpha Receptors ◽  
Factor Alpha ◽  
Toxoplasma Gondii Infection

scholarly journals Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor of Toxoplasma gondii Infection

2021 ◽  
Author(s):  
Nicholas Rinkenberger ◽  
Michael E Abrams ◽  
Sumit K Matta ◽  
John W Schoggins ◽  
Neal M Alto ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Human Cell ◽  
Parasite Growth ◽  
Human Cells ◽  
Human Cell Lines ◽  
Human Pathogen ◽  
Single Factor ◽  
Over Expression ◽  
Interferon Stimulated Genes ◽  
Toxoplasma Gondii Infection

Toxoplasma gondii is an important human pathogen infecting an estimated 1 in 3 people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction interferon stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ mediated immunity to T. gondii infection is a complex, multifactorial process.

scholarly journals Over-expression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Nicholas Rinkenberger ◽  
Michael E Abrams ◽  
Sumit K Matta ◽  
John W Schoggins ◽  
Neal M Alto ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Human Cell ◽  
Parasite Growth ◽  
Human Cells ◽  
Human Cell Lines ◽  
Human Pathogen ◽  
Single Factor ◽  
Over Expression ◽  
Interferon Stimulated Genes ◽  
Toxoplasma Gondii Infection

Toxoplasma gondii is an important human pathogen infecting an estimated 1 in 3 people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction interferon stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ mediated immunity to T. gondii infection is a complex, multifactorial process.

Siparuna guianensis Controls Toxoplasma gondii Infection In Vitro

2021 ◽  
Author(s):  
Laura V. Souza ◽  
Marcos P. O. Almeida ◽  
Neide M. Silva ◽  
Natália C. de Miranda ◽  
Liliane Nebo ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Toxoplasma Gondii Infection

scholarly journals Structural, Functional, and Metabolic Alterations in Human Cerebrovascular Endothelial Cells during Toxoplasma gondii Infection and Amelioration by Verapamil In Vitro

2020 ◽  
Vol 8 (9) ◽  
pp. 1386
Author(s):  
Alaa T. Al-sandaqchi ◽  
Victoria Marsh ◽  
Huw E. L. Williams ◽  
Carl W. Stevenson ◽  
Hany M. Elsheikha
Keyword(s):  
Endothelial Cells ◽  
Toxoplasma Gondii ◽  
Intercellular Junctions ◽  
Proton Nuclear Magnetic Resonance ◽  
Functional Changes ◽  
Brain Infection ◽  
Toxoplasma Gondii Infection ◽  
Cerebrovascular Endothelial Cells ◽  
Treatment Application

Toxoplasma gondii (T. gondii), the causative agent of toxoplasmosis, is a frequent cause of brain infection. Despite its known ability to invade the brain, there is still a dire need to better understand the mechanisms by which this parasite interacts with and crosses the blood–brain barrier (BBB). The present study revealed structural and functional changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. T. gondii proliferated within the BMECs and disrupted the integrity of the cerebrovascular barrier through diminishing the cellular viability, disruption of the intercellular junctions and increasing permeability of the BMEC monolayer, as well as altering lipid homeostasis. Proton nuclear magnetic resonance (1H NMR)-based metabolomics combined with multivariate data analysis revealed profiles that can be attributed to infection and variations in the amounts of certain metabolites (e.g., amino acids, fatty acids) in the extracts of infected compared to control cells. Notably, treatment with the Ca2+ channel blocker verapamil rescued BMEC barrier integrity and restricted intracellular replication of the tachyzoites regardless of the time of treatment application (i.e., prior to infection, early- and late-infection). This study provides new insights into the structural and functional changes that accompany T. gondii infection of the BMECs, and sheds light upon the ability of verapamil to inhibit the parasite proliferation and to ameliorate the adverse effects caused by T. gondii infection.

scholarly journals Cellular apoptosis of HFF cells by inorganic nanoparticles not susceptible to modulation by Toxoplasma gondii infection in vitro

2019 ◽  
Vol 54 ◽  
pp. 280-285 ◽  
Author(s):  
Oluyomi Stephen Adeyemi ◽  
David Adeiza Otohinoyi ◽  
Oluwakemi Josephine Awakan ◽  
Adebukola Anne Adeyanju
Keyword(s):  
Toxoplasma Gondii ◽  
Inorganic Nanoparticles ◽  
Cellular Apoptosis ◽  
Toxoplasma Gondii Infection

scholarly journals Downregulation of the central noradrenergic system by Toxoplasma gondii infection

2018 ◽  
Author(s):  
Isra Alsaady ◽  
Ellen Tedford ◽  
Mohammad Alsaad ◽  
Greg Bristow ◽  
Shivali Kohli ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Neuronal Cells ◽  
Differentially Expressed Gene ◽  
Infection Intensity ◽  
Noradrenergic System ◽  
Motor Impairments ◽  
Plausible Mechanism ◽  
Toxoplasma Gondii Infection ◽  
Human Neuronal Cells

AbstractThe parasitic protozoan Toxoplasma gondii becomes encysted in brain and muscle tissue during chronic infection, a stage that was previously thought to be dormant but has been found to be active and associated with physiological effects in the host. Dysregulation of catecholamines in the CNS has previously been observed in chronically-infected animals. In the study described here, the noradrenergic system was suppressed with decreased levels of norepinephrine in brains of infected animals and in infected neuronal cells in vitro. Expression of dopamine β-hydroxylase (DBH), essential for synthesis of norepinephrine from dopamine, was the most differentially-expressed gene in infections in vitro and was down-regulated in infected brain tissue, particularly in the prefrontal cortex and dorsal locus coeruleus/pons region. The down-regulated DBH expression in infected rat catecholaminergic and human neuronal cells corresponded with decreased norepinephrine and increased dopamine. As the DBH suppression was observed in vitro, this effect is not caused by neuroinflammation. Silencing of DBH expression was specific for T. gondii infection and was not observed with CMV infection. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically-infected animals, with a high correlation between DBH expression and infection intensity. These findings together provide a plausible mechanism to explain prior discrepancies in changes to CNS neurotransmitters levels with infection. The suppression of norepinephrine synthesis observed here may, in part, explain behavioural effects of infection, associations with mental illness, and neurological consequences of infection such as the loss of coordination and motor impairments associated with human toxoplasmosis.

Analogs of marinopyrrole A show enhancement to observed in vitro potency against acute Toxoplasma gondii infection

2021 ◽  
Author(s):  
Matthew C. Martens ◽  
Yan Liu ◽  
Austin G. Sanford ◽  
Alexander I. Wallick ◽  
Rosalie C. Warner ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Acute Infection ◽  
Standard Of Care ◽  
Host Cells ◽  
Infection Model ◽  
Current Standard ◽  
Clinical Consequences ◽  
Toxoplasma Gondii Infection

The apicomplexan parasite Toxoplasma gondii is the causative agent of toxoplasmosis, a globally distributed infection with severe clinical consequences for immunocompromised individuals and developing fetuses. There are few available treatments, and these are associated with potentially severe adverse effects. Marinopyrrole A, a compound discovered in a marine Streptomyces species, has previously been found to exhibit potent antimicrobial activity, prompting our interest in exploring efficacy against Toxoplasma gondii . We found that marinopyrrole A was a highly potent anti- Toxoplasma molecule, with an in vitro 50% maximal inhibitory concentration (IC 50 ) of 0.31 μM corresponding to a higher potency than that of the current standard of care (pyrimethamine); however, addition of 20% serum led to abrogation of potency, and toxicity to human cell lines was observed. Yet, application of marinopyrrole A to an in vivo lethal acute infection model facilitated significantly enhanced survival at doses of 5, 10, and 20 mg/kg. We then tested a series of marinopyrrole A analogs—RL002, RL003, and RL125—demonstrating significantly increased potency in vitro , with IC 50 values ranging from 0.09-0.17 μM (3.6-6.8X increase relative to pyrimethamine). No detectable cytotoxicity was observed up to 50 μM in human foreskin fibroblasts, with cytotoxicity in HepG2 cells ranging from ∼28-50 μM, corresponding to >200X selectivity for parasites over host cells. All analogs additionally showed reduced sensitivity to serum. Further, RL003 potently inhibited in vitro -generated bradyzoites at 0.245 μM. Taken together, these data support further development of marinopyrrole A analogs as promising anti- Toxoplasma molecules to further combat this prevalent infection.

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