Effects of Malaysian strains of Toxoplasma gondii on behaviours and their possible risk in schizophrenia-like rat model

ABSTRACTToxoplasma gondii (T. gondii) is a protozoan parasite that reside majorly in the brain of its intermediate host. T. gondii infected rodent’s shows some degree of behaviour deficits, while T. gondii infection in humans is associated with psychiatric problems such as schizophrenia. The present study aimed to evaluate the effects of Malaysian strains of T. gondii on rats. Forty five, four weeks old, male Wistar rats were used. The rats were assigned into five groups: two control groups (CG1 and CG2) and three experimental groups (EG1, EG2, EG3). CG1 rats received phosphate buffered saline (PBS), CG2 received MK-801 (as a model for schizophrenia), EG1, EG2, EG3 received orally 5 × 103 single T. gondii oocysts strain of type I, type II and type III respectively. After infection, all the five groups of rats were tested for T. gondii antibodies at two weeks post-infection (PI). Behavioural tests of exploratory activity (open field) and spatial learning and memory retention (Morris water maze) were performed on the ninth and tenth weeks PI followed by histological staining of rat brain. T. gondii IgM antibodies were detected in EG1, EG2 and EG3, but not in CG1 and CG2. The behaviour results demonstrated that rats from CG2, EG1, EG2 and EG3 had increased in their locomotor activities and memory deficits compared to control, while learning remain intact. Moreover, tissue cysts were found widely distributed exclusively in the whole brain of EG1, EG2 and EG3 without tropism. These findings taken together, implies that Malaysian strains of T. gondii are implicated in some causes of behaviour changes that are responsible for schizophrenia-like conditions if humans were infected.

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The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

Infection and Immunity ◽

10.1128/iai.00244-18 ◽

2018 ◽

Vol 86 (9) ◽

Cited By ~ 9

Author(s):

Louis-Philippe Leroux ◽

Julie Lorent ◽

Tyson E. Graber ◽

Visnu Chaparro ◽

Laia Masvidal ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Host Cell ◽

Cell Activation ◽

Immune Cell ◽

Mrna Translation ◽

Protozoan Parasite ◽

Translational Efficiency ◽

Type I ◽

Content Type ◽

Infection Inhibition

ABSTRACT The intracellular parasite Toxoplasma gondii promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II T. gondii strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5′-terminal oligopyrimidine (5′ TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed T. gondii replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during T. gondii infection.

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Virulence of atypical Toxoplasma gondii strains isolated in French Guiana in a murine model

Parasite ◽

10.1051/parasite/2019048 ◽

2019 ◽

Vol 26 ◽

pp. 60 ◽

Cited By ~ 2

Author(s):

Stéphane Simon ◽

Benoit de Thoisy ◽

Aurélien Mercier ◽

Mathieu Nacher ◽

Magalie Demar

Keyword(s):

Toxoplasma Gondii ◽

French Guiana ◽

Protozoan Parasite ◽

Type I ◽

Clonal Type ◽

Relevant Animal Model ◽

Wild Strains ◽

Severity Of The Disease ◽

Underlying Mechanisms ◽

Immunocompetent Patients

Background. Toxoplasma gondii is an obligate intracellular protozoan parasite of warm-blooded vertebrates. Most infections in immunocompetent patients are asymptomatic. However, since 2000s, strains with particular genetic profiles that differ from the known clonal type (type I, II, III), have been described. In French Guiana, these strains are highly pathogenic in immunocompetent patients. They have defined a new clinical entity called Amazonian Toxoplasmosis. The present study aims to further improve our knowledge on the pathogenicity of these Amazonian T. gondii strains in comparison with three reference strains using Swiss strain mice. With these data, we tried to establish a predictive virulence score to classify these strains, but also to correlate this virulence with the severity of the disease in infected patients. Results. All the virulence indicators revealed that the Amazonian strains isolated in French Guiana presented a high virulence profile, but lower than the highly virulent type I reference RH strain. The findings reveal differences in virulence between human and animal strains, but also between anthropized and wild strains. Conclusion. In addition to being a clinically relevant animal model of Amazonian Toxoplasmosis, this model could also provide a solid experimental basis for future studies aiming to investigate the underlying mechanisms of Amazonian Toxoplasmosis disease.

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Hydroxylamine and Carboxymethoxylamine Can Inhibit Toxoplasma gondii Growth through an Aspartate Aminotransferase-Independent Pathway

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01889-19 ◽

2020 ◽

Vol 64 (3) ◽

Cited By ~ 1

Author(s):

Jixu Li ◽

Huanping Guo ◽

Eloiza May Galon ◽

Yang Gao ◽

Seung-Hun Lee ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Drug Targets ◽

Protozoan Parasite ◽

Cell Types ◽

Lytic Cycle ◽

Type I ◽

Content Type ◽

Mechanism Of Inhibition

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Plasmodium falciparum. Therefore, AATs are suggested as drug targets against Plasmodium. The T. gondii genome encodes only one predicted AAT in both T. gondii type I strain RH and type II strain PLK. However, the effects of HYD and CAR, as well as their relationship with AAT, on T. gondii remain unclear. In this study, we found that HYD and CAR impaired the lytic cycle of T. gondii in vitro, including the inhibition of invasion or reinvasion, intracellular replication, and egress. Importantly, HYD and CAR could control acute toxoplasmosis in vivo. Further studies showed that HYD and CAR could inhibit the transamination activity of rTgAAT in vitro. However, our results confirmed that deficiency of AAT in both RH and PLK did not reduce the virulence in mice, although the growth ability of the parasites was affected in vitro. HYD and CAR could still inhibit the growth of AAT-deficient parasites. These findings indicated that HYD and CAR inhibition of T. gondii growth and control of toxoplasmosis can occur in an AAT-independent pathway. Overall, further studies focusing on the elucidation of the mechanism of inhibition are warranted. Our study hints at new substrates of HYD and CAR as potential drug targets to inhibit T. gondii growth.

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Nanosilver Colloid Inhibits Toxoplasma gondii Tachyzoites and Bradyzoites in Vitro

Iranian Journal of Parasitology ◽

10.18502/ijpa.v14i3.1474 ◽

2019 ◽

Cited By ~ 1

Author(s):

Saeedeh SHOJAEE ◽

Nima FIROUZEH ◽

Hussein KESHAVARZ ◽

Sanaz JAFARPOUR AZAMI ◽

Mahboobeh SALIMI ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Structural Changes ◽

Protozoan Parasite ◽

Blue Dye ◽

Type I ◽

Worldwide Distribution ◽

Life Threatening ◽

Strain Type ◽

In Vitro Effects

Background: Toxoplasma gondii, the coccidian protozoan parasite with worldwide distribution, is the agent of toxoplasmosis. The disease is life threatening in congenital form and in immunocompromised patients. The present study was carried out in 2016 to evaluate the in vitro effects of nanosilver colloid on tachyzoites and bradyzoites of T. gondii, RH and Tehran strains. Methods: Different concentrations (5, 10 , 20 ppm) of nanosilver colloid were added to tachyzoites of T. gondii , RH strain (type I) and bradyzoites and tissue cysts of T. gondii , Tehran strain (type II) and incubated for 30, 60, 90 and 120 minutes. The mortality rates of tachyzoites and bradyzoites were evaluated by trypan blue dye and MTT assay. Then SEM carried out to show the changes between control and exposed parasites. Results: The greatest mortality rate was seen in 20 ppm concentration and after 120 minutes of exposure. By electron microscopy, the structural changes were seen in tachyzoites of RH and tissue cyst of Tehran strain in comparison with control groups. Conclusion: Nanosilver colloid was effective on both tachyzoites and bradyzoites of T. gondii, RH and Tehran strains.

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Toxoplasmosis

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070804_update_005 ◽

2010 ◽

pp. 1090-1097

Author(s):

Oliver Liesenfeld ◽

Eskild Petersen

Keyword(s):

Polymerase Chain Reaction ◽

Toxoplasma Gondii ◽

Direct Detection ◽

Protozoan Parasite ◽

Human Infection ◽

Clinical Samples ◽

Worldwide Distribution ◽

Polymerase Chain ◽

The Brain ◽

Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection may be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction, PCR) or by serological techniques....

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Toxoplasmosis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0162 ◽

2020 ◽

pp. 1416-1424

Author(s):

Oliver Liesenfeld ◽

Eskild Petersen

Keyword(s):

Polymerase Chain Reaction ◽

Toxoplasma Gondii ◽

Direct Detection ◽

Protozoan Parasite ◽

Human Infection ◽

Clinical Samples ◽

Worldwide Distribution ◽

Polymerase Chain ◽

The Brain ◽

Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection can be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction) or by serological techniques.

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CD11c- and CD11b-expressing mouse leukocytes transport single Toxoplasma gondii tachyzoites to the brain

Blood ◽

10.1182/blood-2005-02-0666 ◽

2006 ◽

Vol 107 (1) ◽

pp. 309-316 ◽

Cited By ~ 239

Author(s):

Nathalie Courret ◽

Sylvie Darche ◽

Pierre Sonigo ◽

Geneviève Milon ◽

Dominique Buzoni-Gâtel ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Fluorescent Protein ◽

Ex Vivo ◽

Protozoan Parasite ◽

Blood Parasites ◽

Cell Periphery ◽

Mesenteric Lymph Nodes ◽

Cell Plasma ◽

Green Fluorescent ◽

The Brain

AbstractThe protozoan parasite Toxoplasma gondii enters hosts through the intestinal mucosa and colonizes distant tissues such as the brain, where its progeny persists for a lifetime. We investigated the role of CD11c- and CD11b-expressing leukocytes in T gondii transport during the early step of parasitism from the mouse small intestine and during subsequent parasite localization in the brain. Following intragastric inoculation of cyst-containing parasites in mice, CD11c+ dendritic cells from the intestinal lamina propria, the Peyer patches, and the mesenteric lymph nodes were parasitized while in the blood, parasites were associated with the CD11c- CD11b+ monocytes. Using adoptive transfer experiments, we demonstrated that these parasitized cells triggered a parasitic process in the brain of naive recipient mice. Ex vivo analysis of parasitized leukocytes showed that single tachyzoites remained at the cell periphery, often surrounded by the host cell plasma membrane, but did not divide. Using either a dye that labels circulating leukocytes or an antibody known to prevent CD11b+ circulating leukocytes from leaving the microvascular bed lumen, and chimeric mice in which the hematopoietic cells expressed the green fluorescent protein, we established that T gondii zoites hijacked CD11b+ leukocytes to reach the brain extravascular space.

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ILC1-derived IFN-γ mediates cDC1-dependent host resistance against Toxoplasma gondii

10.1101/2020.01.06.895771 ◽

2020 ◽

Author(s):

Américo H. López-Yglesias ◽

Elise Burger ◽

Ellie Camanzo ◽

Andrew T. Martin ◽

Alessandra M. Araujo ◽

...

Keyword(s):

Immune Response ◽

Transcription Factor ◽

Toxoplasma Gondii ◽

Host Resistance ◽

Protozoan Parasite ◽

Protective Role ◽

Type I ◽

Intracellular Pathogens ◽

Ifn Γ ◽

Parasitic Pathogens

ABSTRACTHost resistance against intracellular pathogens requires a rapid IFN-γ mediated immune response. We reveal that T-bet-dependent production of IFN-γ is essential for the maintenance of inflammatory DCs at the site of infection with a common protozoan parasite, Toxoplasma gondii. A detailed analysis of the cellular sources for T-bet-dependent IFN-γ identified that ILC1s, but not NK or TH1 cells, were involved in the regulation of inflammatory DCs via IFN-γ. Mechanistically, we established that T-bet dependent ILC1-derived IFN-γ is critical for the induction of IRF8, an essential transcription factor for cDC1s. Failure to upregulate IRF8 in DCs resulted in acute susceptibility to T. gondii infection. Our data identifies that ILC1-derived IFN-γ is indispensable for host resistance against intracellular infection via maintaining IRF8+ inflammatory DCs at the site of infection.Author SummaryMounting a robust type I innate immune response is essential for resistance against numerous intracellular pathogens. The type I immune response is characterized by the production of IFN-γ, a central cytokine required for multiple non-redundant effector functions against bacterial, viral, and parasitic pathogens. Previous work has shown that group 1 innate lymphocyte cells (ILC1s) together with NK and CD4+ T cells play an indispensable IFN-γ mediated protective role against Toxoplasma gondii infection; yet, the pathway of how IFN-γ produced by ILC1s defend against T. gondii remains unknown. In this work we identified that early production of IFN-γ by ILC1 is essential for maintaining dendritic cells (DCs) during infection. Mechanistically, we reveal that ILC1-derived IFN-γ is indispensable for inducing the transcription factor IRF8 that is critical for sustaining inflammatory DCs. Finally, we demonstrate that IRF8+ DCs are critical for parasite elimination.

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Neurotoxicity and Immunotoxicity Assessment in CBA/J Mice with Chronic Toxoplasma gondii Infection and Single-Dose Exposure to Methylmercury

International Journal of Toxicology ◽

10.1080/10915810305075 ◽

2003 ◽

Vol 22 (1) ◽

pp. 53-61 ◽

Cited By ~ 6

Author(s):

Marquea D. King ◽

David S. Lindsay ◽

Steven Holladay ◽

Marion Ehrich

Keyword(s):

Body Weight ◽

Single Dose ◽

T Cell ◽

Toxoplasma Gondii ◽

Histopathological Examination ◽

Synergistic Effects ◽

Protozoan Parasite ◽

Cell Subpopulations ◽

T Cell Subpopulations ◽

The Brain

Toxoplasma gondii is a protozoan parasite that localizes in the brain where it can cause life-threatening disease. Methylmercury (Me Hg) is a well-documented neurotoxicant that accumulates in the brain. We investigated end points associated with immunotoxicity and neurotoxicity in mice exposed to Me Hg during a chronic T. gondii infection. Two groups of 6-week-old, female CBA/J mice were either fed 25 T. gondii tissue cysts of the ME-49 strain or given vehicle. Six weeks later, half of the mice in each group were orally gavaged with a single dose of 20 mg/kg body weight of Me Hg, creating four groups of mice (vehicle control, T. gondii, Me Hg, and T. gondii/Me Hg). Mice were sacrificed 7 days post Me Hg exposure. Me Hg exposure caused a significant decrease in mouse body weight. Me Hg administration resulted in an increase of splenic cellularity and spleen-to-body weight ratios. Me Hg had no significant effect on the percentages of CD4+, CD8+, or non-T-cell subpopulations in the spleen. Me Hg dosed mice demonstrated an increase in absolute numbers of splenic CD4+, CD8+, or non-T cells when compared to mice in control and T. gondii-infected groups. Thymic CD4+CD8+ T-cell subpopulations were decreased ( p <.05) by Me Hg with or without a concurrent T. gondii infection. There was a significant ( p <.05) increase in brain tissue cyst counts within the group exposed to both Me Hg and T. gondii (16 4, mean SE, n = 7) versus T. gondii alone (4 1, n = 8). Histopathological examination demonstrated encephalitis, gliosis, and meningitis in brains from mice infected with T. gondii. These data indicate that exposure to both Me Hg and T. gondii has synergistic effects, with effects of Me Hg especially on the immune system.

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Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

Pathogens ◽

10.3390/pathogens10111351 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1351

Author(s):

Darine Daher ◽

Ahmad Shaghlil ◽

Eyad Sobh ◽

Maguy Hamie ◽

Malika Elhage Hassan ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Protozoan Parasite ◽

Etiologic Agent ◽

Treatment Modalities ◽

Comprehensive Overview ◽

Associated Diseases ◽

Threatening Condition ◽

Life Threatening ◽

Acute Toxoplasmosis ◽

The Brain

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms. Acute toxoplasmosis presents as mild or asymptomatic disease that evolves, under the host immune response, into a persistent chronic disease in healthy individuals. Chronic toxoplasmosis establishes as latent tissue cysts in the brain and skeletal muscles. In immunocompromised patients, chronic toxoplasmosis may reactivate, leading to a potentially life-threatening condition. Recently, the association between toxoplasmosis and various diseases has been shown. These span primary neuropathies, behavioral and psychiatric disorders, and different types of cancer. Currently, a direct pre-clinical or clinical molecular connotation between toxoplasmosis and most of its associated diseases remains poorly understood. In this review, we provide a comprehensive overview on Toxoplasma-induced and associated diseases with a focus on available knowledge of the molecular players dictating these associations. We will also abridge the existing therapeutic options of toxoplasmosis and highlight the current gaps to explore the implications of toxoplasmosis on its associated diseases to advance treatment modalities.

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