Thursday, May 05, 2016

Influence of Toxoplasma Gondii Infection on Symptoms and Signs of Menopause

2016 Jan 27;6(1):49-55. doi: 10.1556/1886.2015.00050. eCollection 2016.


Some symptoms of menopause have also been described in patients with toxoplasmosis. Whether Toxoplasma gondii (T. gondii) infection has any influence on clinical manifestations of menopause is yet unknown. We sought to determine whether T. gondii exposure is associated with symptoms and signs of menopause. We performed a cross-sectional study of women attending a public health center in Durango City, Mexico. Participants were examined for the presence of anti-Toxoplasma IgG and IgM antibodies using enzyme-linked immunoassays. A questionnaire including 47 symptoms and signs potentially associated with menopause was applied. Association of seroprevalence for T. gondii with clinical characteristics of women was assessed by bivariate and multivariate analyses. Bivariate analysis showed that bouts of rapid heartbeat, breast pain, electric shock sensation, dizziness, digestive problems, low back pain, and migraine were associated with seropositivity to either IgG anti-T. gondii alone or both IgG and IgM anti-T. gondii. Breast pain was the only variable that was found to be associated with IgG seropositivity to T. gondii by multivariate analysis: (OR = 2.84; 95% CI: 1.35-5.90; P = 0.005). Our results suggest that T. gondii exposure may influence on the clinical manifestations of menopause. Results deserve further research.

KEYWORDS:

Toxoplasma gondii; cross-sectional study; menopause; perimenopause; seroprevalence
PMID:
27141314
[PubMed]

Attenuated Toxoplasma gondii therapy of disseminated pancreatic cancer generates long-lasting immunity to pancreatic cancer

2015 Oct 29;5(4):e1104447. eCollection 2016.


We have recently reported that treatment of disseminated pancreatic cancer with an attenuated Toxoplasma gondii uracil auxotroph vaccine promoted antitumor CD8+ T cell responses and long-term survival. Here, we optimized the treatment strategy for disseminated pancreatic cancer and show that attenuated Toxoplasma gondii therapy stimulated effective long-term immunity to pancreatic cancer through mechanisms involving CD4+ T cells and pancreatic tumor-specific IgG. Our results suggest that cell-mediated immunity in conjunction with humoral antibody immunity may offer greater resistance to recurrence of highly aggressive tumors. Cancer immunotherapeutic strategies using attenuated Toxoplasma gondii vaccines merit further investigation as a novel strategy to reawaken immunity to primary pancreatic carcinoma and to generate long-lasting immunity to pancreatic cancer recurrences.

KEYWORDS:

Humoral immunity; T cell protection; Toxoplasma gondii; immunotherapy; pancreatic cancer; tumor-specific antibodies
PMID:
27141388
[PubMed]

Epigenetics: A New Model for Intracellular Parasite-Host Cell Regulation

2016 Apr 30. pii: S1471-4922(16)30005-8. doi: 10.1016/j.pt.2016.04.002. [Epub ahead of print]


Intracellular protozoan parasites are an extremely important class of pathogens that cause a spectrum of diseases in human and animal hosts. There is a growing body of evidence suggesting that protozoan parasites, like other prokaryotic and viral pathogens, manipulate host cells via epigenetic modifications of the host genome that alter transcription and corresponding signaling pathways. In light of these data, we examine the role of epigenetics in downregulation of host macrophages by Leishmania that could potentially lead to a permanent state of inactivation, thus favoring pathogen survival and disease progression.
Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS:

DNA methylation; Leishmania; Theileria; Toxoplasma; epigenetics; exosomes.; histone modification; ncRNA
PMID:
27142564
[PubMed - as supplied by publisher]

Saturday, April 30, 2016

The impact of Toxoplasma gondii on the mammalian genome

 2016 Apr 26;32:19-25. doi: 10.1016/j.mib.2016.04.009. [Epub ahead of print]

Abstract

Nobody doubts that infections have imposed specialisations on the mammalian genome. However sufficient information is usually missing to attribute a specific genomic modification to pressure from a specific pathogen. Recent studies on mechanisms of mammalian resistance against the ubiquitous protozoan parasite, Toxoplasma gondii, have shown that the small rodents presumed to be largely responsible for transmission of the parasite to its definitive host, the domestic cat, possess distinctive recognition proteins, and interferon-inducible effector proteins (IRG proteins) that limit the potential virulence of the parasite. The phylogenetic association of the recognition proteins, TLR11 and TLR12, with T. gondii resistance is weak, but there is evidence for reciprocal polymorphism between parasite virulence proteins and host IRG proteins that strongly suggests current or recent coevolution.
Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
PMID:
 
27128504
 
[PubMed - as supplied by publisher]

Friday, April 29, 2016

Toxoplasma gondii infection and schizophrenia: an inter-kingdom communication perspective

2016 Jun;29(3):311-8. doi: 10.1097/QCO.0000000000000265.


PURPOSE OF REVIEW:

The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the central nervous system and has been suggested as a risk factor for schizophrenia. Here, we address some of the mechanisms by which T. gondii achieves this by manipulating signaling pathways of the host brain cells.

RECENT FINDINGS:

Recent years have brought notable progress in the understanding of how the opportunistic parasite T. gondii establishes a successful infection in mammalian brain by secreting effector molecules that manipulate multiple cell functions. Many pathways involved in this inter-kingdom signaling, such as dopaminergic, GABAergic and kynurenine pathways, also have key roles in the development of schizophrenia. More understanding of T. gondii-brain cell interaction holds the key to unlocking the mystery of T. gondii-mediated schizophrenia pathogenesis.

SUMMARY:

T. gondii usurps a variety of host signaling pathways to ensure physiological adaptation, evasion of host immune defense systems, and efficient replication. A detailed knowledge of T. gondii signaling molecules involved in this cross-kingdom communication with host brain cells will probably provide novel means of pharmacologically manipulating host cellular pathways to promote efficient elimination of the parasite and may permit the development of new schizophrenia-modifying therapeutics.
PMID:
27120002
[PubMed - in process]

Behavioral Abnormalities in a Mouse Model of Chronic Toxoplasmosis Are Associated with MAG1 Antibody Levels and Cyst Burden

2016 Apr 28;10(4):e0004674. doi: 10.1371/journal.pntd.0004674. eCollection 2016.


There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human.
PMID:
27124472
[PubMed - as supplied by publisher]

Tuesday, April 26, 2016

Toxoplasmosis and Alzheimer: can Toxoplasma gondii really be introduced as a risk factor in etiology of Alzheimer?

 2016 Apr 23. [Epub ahead of print]

Abstract

Alzheimer is a progressive neurological disease that results in irreversible loss of neurons and includes about two thirds of all cases of dementia. Toxoplasma gondii may be an important infectious agent involved in neurodegenerative diseases. The aim of this study was to investigate the correlation between Toxoplasma as an etiologic agent in the progress of Alzheimer's disease. This case control study was conducted on 75 Alzheimer's patients and 75 healthy volunteers. Blood samples were obtained and anti-Toxoplasma IgG and IgM tests were done by using ELISA technique. DNA was extracted from buffy coat and then GRA6 gene and SAG2 loci were amplified by PCR and nested PCR, respectively. Chi-square, Fisher's test, and binary logistic regression were used for data analysis. A percentage of 61.3 % of Alzheimer's patients and 62.6 % of healthy volunteers were positive for anti-Toxoplasma IgG but all participants were negative for anti-Toxoplasma IgM. There were no significant differences between Alzheimer's patients with their controls in terms of anti-Toxoplasma IgG antibody (P = 0.5). Due to lack of positive IgM sample, results of the molecular methods were negative by GRA6 and SAG2 fragments amplification. This result shows that, infection with T. gondii cannot be considered as a risk factor for etiology and developing Alzheimer's disease.

KEYWORDS:

Alzheimer’s disease; ELISA; Iran; PCR; Toxoplasma gondii
PMID:
 
27106237
 
[PubMed - as supplied by publisher]

Toxoplasma gondii: Effects of diphenyl diselenide in experimental toxoplasmosis on biomarkers of cardiac function

 2016 Apr 20. pii: S0014-4894(16)30076-5. doi: 10.1016/j.exppara.2016.04.014. [Epub ahead of print]

Abstract

This study aimed to investigate the effects of diphenyl diselenide (PhSe)2 to treat mice experimentally infected by Toxoplasma gondii on seric biomarkers of cardiac function (creatine kinase, creatine kinase MB, troponin, and myoglobin), and lactate dehydrogenase, as well as to evaluate the enzymatic activity of creatine kinase (CK) and adenylate kinase (AK) in heart tissue. For the study, 40 female mice were divided into four groups of 10 animals each: the group A (uninfected and untreated), the group B (uninfected and treated), the group C (infected and untreated) and the group D (infected and treated). The inoculation was performed with 50 cysts of T. gondii (ME-49 strain). Mice from groups B and D were treated at days 1 and 20 post-infection (PI) with 5 μmol kg-1 of (PhSe)2 subcutaneously. On day 30 PI, the mice were anesthetized and euthanized for blood and heart collection. As a result, it was observed a decrease in AK activity (P < 0.01) in the heart samples of groups C and D compared to the group A. Cardiac CK increased in the group C compared to the group A (P < 0.01). CK levels increased in infected mice (the group C) compared to other groups (A and D). Regarding CK-MB level, there was a decrease in the group D compared to the group B, without statistical difference compared to control groups (A and C). It was observed an increase on myoglobin in groups C and D, differently of troponin, which did not show statistical difference (P < 0.05) between groups. Mice from the group C showed an increase in lactate dehydrogenase (LDH) levels compared to other groups (A, B, and D). Histopathological evaluation of heart samples revealed necrosis, hemorrhagic regions and inflammatory infiltrates in mice from the Group C, differently from the group D where animals showed only inflammatory infiltrates. Based on these results we conclude that the (PhSe)2 had a protective effect on the heart in experimental toxoplasmosis by modulating tissue and seric CK activity, and avoiding an increase on seric LDH levels, probably due to the antioxidant effect of this compound.
Copyright © 2016. Published by Elsevier Inc.

KEYWORDS:

Adenylate kinase; Creatine kinase; Creatine kinase-MB; Lactate dehydrogenase; Myoglobin; Toxoplasma gondii; Troponin
PMID:
 
27107930
 
[PubMed - as supplied by publisher]

Cerebral complement C1q activation in chronic Toxoplasma infection

 2016 Apr 21. pii: S0889-1591(16)30100-3. doi: 10.1016/j.bbi.2016.04.009. [Epub ahead of print]

Abstract

Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary,our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.
Copyright © 2016. Published by Elsevier Inc.

KEYWORDS:

Glia; MAG1 antibodies; Neurons; Prefrontal cortex; Psychiatry; Toxoplasmosis
PMID:
 
27109609
 
[PubMed - as supplied by publisher]

Thursday, April 21, 2016

Functional analysis of Toxoplasma gondii Nucleoside Triphosphate Hydrolases I and II in acute mouse virulence and immune suppression

 2016 Apr 18. pii: IAI.00077-16. [Epub ahead of print]

Abstract

Bioluminescent reporter assays have been widely used to study the effect ofToxoplasma gondiion host gene expression. In the present study we extend these studies by engineering novel reporter cell lines containing a gamma activated sequence (GAS) element driving Firefly luciferase (FLUC). In RAW264.7 macrophages,T. gondiitype I strain (GT1) infection blocked interferon-gamma (IFN-γ) induced FLUC activity to a significantly greater extent than infection by type II (ME49) and type III (CTG) strains. Quantitative trait locus (QTL) analysis of progeny from a prior genetic cross identified a genomic region on chromosome XII that correlated with the observed strain-dependent phenotype. This QTL region contains two isoforms of theT. gondiienzyme Nucleoside Triphosphate Hydrolase (NTPase) that were the prime candidates for mediating the observed strain-specific effect. Using reverse genetic analysis we show that deletion of NTPase I from a type I strain (RH) background restored the higher luciferase levels seen in the type II (ME49) strain. Rather than an effect on IFN-γ-dependent transcription, our data suggest that NTPase I was responsible for the strain-dependent difference in FLUC activity due to hydrolysis of ATP. We further show that NTPase I and II were not essential for tachyzoite growthin vitroor virulence in mice. Our study reveals that whileT. gondiiNTPases are not essential for immune evasion, they can affect ATP-dependent reporters. Importantly, this limitation was overcome using an ATP independent Gaussia luciferase (GLUC), which provides a more appropriate reporter for use withT. gondiiinfection studies.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PMID:
 
27091930
 
[PubMed - as supplied by publisher]

Tuesday, April 19, 2016

CD8+ T cells remove cysts of Toxoplasma gondii from the brain mostly by recognizing epitopes commonly expressed by or cross-reactive between type II and type III strains of the parasite

2016 Apr 12. pii: S1286-4579(16)30025-9. doi: 10.1016/j.micinf.2016.03.013. [Epub ahead of print]


Our previous study demonstrated that CD8+ T cells remove cysts of Toxoplasma gondii from the brain through perforin-mediated mechanisms. We here show that a transfer of CD8+ immune T cells primed with a type II or a type III strain of T. gondii both efficiently removed cysts of a type II strain from infected SCID mice, although the former tended to be slightly more efficient than the latter. Similarly, a transfer of type II-primed CD8+ T cells removed cysts of a type III strain. Therefore, CD8+ T cells are capable of removing T. gondii cysts by recognizing epitopes commonly expressed in types II and III strains or cross-reactive between these two genotypes.
Copyright © 2016. Published by Elsevier Masson SAS.

KEYWORDS:

CD8(+) T cells; Toxoplasma gondii; cyst; genotype; perforin
PMID:
27083473
[PubMed - as supplied by publisher]

Use of human induced pluripotent stem cell-derived neurons as a model for Cerebral Toxoplasmosis

2016 Apr 12. pii: S1286-4579(16)30024-7. doi: 10.1016/j.micinf.2016.03.012. [Epub ahead of print]


Toxoplasma gondii is a ubiquitous protozoan parasite with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides primarily in cysts within neurons in the central nervous system. The chronic infection in immunocompetant individuals has been considered to be asymptomatic but increasing evidence indicates the chronic infection can lead to neuropsychiatric disorders such as Schizophrenia, prenatal depression and suicidal thoughts. A better understanding of the mechanism(s) by which the parasite exerts effects on human behavior is limited due to lack of suitable human neuronal models. In this paper, we report the use of human neurons derived from normal cord blood CD4+ cells generated via genetic reprogramming, as an in vitro model for the study T. gondii in neurons. This culture method resulted in a relatively pure monolayer of induced human neuronal-like cells that stained positive for neuronal markers, MAP2, NFL, NFH and NeuN. These induced human neuronal-like cells (iHNs) were efficiently infected by the Prugniad strain of the parasite and supported replication of the tachyzoite stage and development of the cyst stage. Infected iHNs could be maintained through 5 days of infection, allowing for formation of large cysts. This induced human neuronal model represents a novel culture method to study both tachyzoite and bradyzoite stages of T. gondii in human neurons.
Copyright © 2016. Published by Elsevier Masson SAS.

KEYWORDS:

Cysts; Induced Neuronal Cells; latent toxoplasmosis
PMID:
27083472
[PubMed - as supplied by publisher]

Saturday, April 16, 2016

Association Between Toxoplasma gondii Exposure and Heart Disease: A Case-Control Study

 2016 May;8(5):402-9. doi: 10.14740/jocmr2525w. Epub 2016 Mar 20.

Abstract

BACKGROUND: 

The parasite Toxoplasma gondii causes infections all around the world. Infections with T. gondii are systemic and the parasite can persist in the heart muscle. Very little is known about the impact of T. gondii on patients with heart disease. We determined the association between T. gondii exposure and patients suffering from heart diseases attending in a public hospital in Durango, Mexico; the association of T. gondii exposure with socio-demographic, behavioral, and clinical characteristics of these patients was also investigated.

METHODS: 

Through a case-control study, we examined the seroprevalence of anti-T. gondii IgG and IgM antibodies in 400 patients with heart diseases and 400 age- and gender-matched controls using enzyme-linked immunoassays. In addition, we analyzed the association of patient characteristics as determined by a standardized questionnaire with T. gondii exposure by bivariate and multivariate analyses.

RESULTS: 

Fifty-five (13.8%) of 400 patients and 32 (8.0%) of 400 controls had anti-T. gondii IgG antibodies (odds ratio (OR) = 1.83; 95% confidence interval (CI): 1.15 - 2.90; P = 0.01). High anti-T. gondii IgG levels (> 150 IU/mL) were found in 28 (50.9%) of the 55 positive cases and in 14 (43.8%) of the 32 positive controls (P = 0.51). Anti-T. gondii IgM antibodies were found in 13 (23.6%) of the 55 anti-T. gondii IgG positive patients and in 19 (59.4%) of 32 anti-T. gondii IgG positive controls (OR = 0.21; 95% CI: 0.08 - 0.54; P = 0.0008). Multivariate analysis showed that T. gondii exposure was positively associated with being born out of Durango State (OR = 2.93; 95% CI: 1.40 - 6.13; P = 0.004), and with consumption of alcohol (OR = 2.04; 95% CI: 1.01 - 4.12; P = 0.04).

CONCLUSIONS: 

Results obtained in this study indicate that T. gondii infection is associated with heart disease, and suggest that heart disease might be related with a chronic infection. This is the first report of an association of T. gondii exposure with alcohol consumption in this population. Results warrant for further research to determine the epidemiological impact of T. gondii exposure on patients with heart diseases. Risk factors associated with T. gondii exposure are critical to design future prevention strategies against T. gondii exposure.

KEYWORDS: 

Alcohol; Case-control study; Epidemiology; Heart disease; Seroprevalence; Toxoplasma gondii
PMID:
 
27081427
 
[PubMed]

Investigating the Determinants of Toxoplasma gondii Prevalence in Meat: A Systematic Review and Meta-Regression

 2016 Apr 15;11(4):e0153856. doi: 10.1371/journal.pone.0153856.

Abstract

BACKGROUND: 

Toxoplasma gondii is one of the most widespread parasites in humans and can cause severe illness in immunocompromised individuals. However, its role in healthy people is probably under-appreciated. The complex epidemiology of this protozoan recognizes several infection routes but consumption of contaminated food is likely to be the predominant one. Among food, consumption of raw and undercooked meat is a relevant route of transmission, but the role of different meat producing animal species and meats thereof is controversial.

OBJECTIVES: 

The aim of the present work is to summarize and analyse literature data reporting prevalence estimates of T. gondii in meat animals/meats.

DATA SOURCES: 

We searched Medline, Web of Science, Science Direct (last update 31/03/2015).

ELIGIBILITY CRITERIA: 

Relevant papers should report data from primary studies dealing with the prevalence of T. gondii in meat from livestock species as obtained through direct detection methods. Meta-analysis and meta-regression were performed.

RESULTS: 

Of 1915 papers screened, 69 papers were included, dealing mainly with cattle, pigs and sheep. Pooled prevalences, based on random-effect models, were 2.6% (CI95 [0.5-5.8]) for cattle, 12.3% (CI95 [7.6-17.8]) for pigs and 14.7% (CI95 [8.9-21.5]) for sheep. Due to the high heterogeneity observed, univariable and multivariable meta-regression models were fitted showing that the geographic area for cattle (p = 0.032), the farming type for pigs (p = 0.0004) and the sample composition for sheep (p = 0.03) had significant effects on the prevalences of Toxoplasma detected/estimated. Moreover, the role of different animal species was dependent on the geographic location of animals' origin.

LIMITATIONS: 

Limitations were due mainly to a possible publication bias.

CONCLUSIONS AND IMPLICATIONS: 

The present work confirms the role of meat, including beef, as T. gondii sources, and highlights the need for a control system for this parasite to be implemented along the meat production chain. Moreover, consumer knowledge should be strengthened in order to reduce the impact of disease.
PMID:
 
27082633
 
[PubMed - as supplied by publisher]