Toxoplasmosis Research Articles

Determination of parasitic burden in the brain tissue of infected mice in acute toxoplasmosis after treatment by fluconazole combined with sulfadiazine and pyrimethamine

Background/aimsOne of the opportunistic pathogens which cause serious problems in the human immune system is Toxoplasma gondii, with toxoplasma encephalitis (TE) seen in patients affected by it. The treatment of these patients is limited, and if not treated on time, death will be possible.MethodsIn this study, the effects of the treatment with different doses of fluconazole (FLZ) in combination with the current treatment of acute toxoplasmosis on reducing the mortality rate and the parasitic load in the murine model in vivo were studied. The mice were treated with different doses of fluconazole alone, sulfadiazine, and pyrimethamine plus fluconazole. A day after the end of the treatment and 1 day before death, the mice’s brains were collected, and after DNA extraction and molecular tests, the parasite burden was detected.ResultsThis study showed that a 10-day treatment with 20 mg/kg of fluconazole combined with sulfadiazine and pyrimethamine 1.40 mg/kg per day affected acute toxoplasmosis and reduced the parasitic load significantly in brain tissues and also increased the survival rate of all mice in this group until the last day of the study, in contrast to other treatment groups. These results also indicate the positive effects of combined therapy on Toxoplasma gondii and the prevention of relapse.ConclusionsReducing the parasitic burden and increasing the survival rate were more effective against acute toxoplasmosis in the combined treatment of different doses of fluconazole with current treatments than current treatments without fluconazole. In other words, combination therapy with fluconazole plus pyrimethamine reduced the parasitic burden in the brain significantly, so it could be a replacement therapy in patients with intolerance sulfadiazine.

A Study of Association of Toxoplasma gondii Infection With Schizophrenia in Mashhad Area, Khorasan Razavi Province, Iran

Background and aims: Congenital toxoplasmosis is assumed to play a role in developing schizophrenia in human. This study aimed to estimate the relationship between Toxoplasma infection and schizophrenia by using enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR).Methods: In this case-control study, 46 schizophrenic patients forming our case group as well as 40 healthy relatives of schizophrenic patients forming our control group were selected from among 456 inpatients with schizophrenia in Ibn Sina and Hejazi hospitals in Mashhad from June 2016 to February 2017. The blood samples from both groups were collected for serological and molecular tests. Different statistical methods such as Chi-square, independent t test, and logistic regression models were used in the present study.Results: In the present study, the seroprevalence of T. gondii was 54% in case group and 45% in control (OR=1.44, 95% CI: 062- 3.40, P = 0.38). There was no significant association between the seroprevalence of T. gondii infection and age, gender, and season as the risk factors in the case group. Furthermore, a poor agreement was observed between the microscopy and PCR methods. Non-significant differences were found between the mean levels of interferon gamma (IFN-γ), C-reactive protein (CRP), and white blood cell (WBC) in two groups. Conclusion: Contrary to the reports from some studies, no association was found between Toxoplasma infection and the schizophrenia. In order to better understand the effect of Toxoplasma on schizophrenia, it is necessary to develop laboratory methods to differentiate acquired toxoplasmosis from congenital one.

The challenges of treating a patient with recurrent congenital toxoplasmic chorioretinitis

Abstract Congenital toxoplasmosis is a rare, non-curable parasite infection, that affects approximately 242 children in Europe each year. Poland has one of the highest rates of congenital toxoplasmosis in Europe. Transmission of Toxoplasma gondii to the fetus results in numerous medical conditions, such as developmental delay, intellectual disabilities, seizures, hearing loss, and blindness. Chorioretinitis is a serious manifestation of congenital toxoplasmosis that can recur even after 25 years from the primary infection, which poses a significant therapeutic challenge. A 41-year-old female reported to the Ophthalmology Emergency Room due to blurred vision and pain in the right eye, accompanied by a constant headache. The patient suffered from congenital toxoplasmosis with two relapses in the past. On examination, the best-corrected visual acuity was 1,0 in both eyes, and the intraocular pressure was significantly increased. Slit-lamp examination showed vitritis and an active retinochoroidal lesion in the right eye. In the left eye, there was a retinochoroidal scar. A relapse of toxoplasmosis was suspected. Serology for Toxoplasma gondii was positive. Pyrimethamine with sulfadiazine, clindamycin, topical corticosteroids, and intraocular pressure-lowering drugs were implemented. During the treatment, the patient developed corticonuclear cataract in both eyes and reported psychotic symptoms. Clinical condition improved after the treatment with corticosteroids at a lower dose. Treatment of ocular manifestations of congenital toxoplasmosis is challenging. The clinical benefit of treatment should be weighed against side effects for each patient. Running title: Congenital toxoplasmosis treatment

Congenital toxoplasmosis in humans: an update of worldwide rate of congenital infections.

The morbidity due to congenital toxoplasmosis in humans is very high. Most of these infected children are likely to develop symptoms of clinical toxoplasmosis. Sequelae in fetus resulting from Toxoplasma gondii infections in women who become infected with this parasite during pregnancy can be devastating and enormous efforts are directed in some countries to prevent these consequences. Here, an update on congenital toxoplasmosis in humans, especially the rate of congenital infections in humans worldwide, is provided. Although several countries have surveillance programmes, most information on the rate of congenital transmission is from France and Brazil. Because of compulsory national screening programme in France to detect and treat women with recently acquired T. gondii infection with anti-toxoplasma therapy, the rate of congenital transmission and the severity of disease in children are declining. Infections by this parasite are widely prevalent in Brazil. The severity of clinical toxoplasmosis in Brazilian children is very high and may be associated with the genetic characteristics of T. gondii isolates prevailing in animals and humans in Brazil. Virtually little or no information is available on this topic from China, India and other countries in Asia.

Epidemiological Aspects of Maternal and Congenital Toxoplasmosis in Panama.

In Panama, epidemiological data on congenital toxoplasmosis are limited, making it difficult to understand the scope of clinical manifestations in the population and factors that may increase the risk of infection. This study provides insight into the epidemiological situation of maternal and congenital toxoplasmosis in Panama and contributing information on the burden of this disease in Central America. Blood samples were collected from 2326 pregnant women and used for the detection of anti-T. gondii antibodies. A high seroprevalence (44.41%) was observed for T. gondii infection in pregnant women from different regions of Panama, with an estimated incidence rate of congenital toxoplasmosis of 3.8 cases per 1000 live births. The main risk factors associated with T. gondii infection using bivariate statistical analysis were an elementary level education and maternal age range of 34-45 years. Multivariate statistical analyses revealed that in some regions (San Miguelito, North and West regions), the number of positive cases correlated with the presence of pets, stray dogs and the consumption of poultry. In other regions (East and Metropolitan regions), the absence of pets was considered a protective factor associated with negative cases, while the presence of stray cats and the age range of 25–34 years did not represent any risk in these regions.

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-β1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.

Current Treatment and Primary Prophylaxis for Toxoplasmosis


 
 
 
 Background: Toxoplasmosis is still a health problem in the world. This parasite is found cosmopolitan in humans and animals. In Indonesia, the prevalence of positive anti-Toxoplasma gondii substances in humans ranges from 2-63%, but there are still few comprehensive studies on current treatment and prophylaxis to treat it.
 Objective: This article will provide an in-depth review of current treatment and primary prophylaxis in toxoplasmosis.
 Methods: Searching the latest literature, obtained 10 relevant journals.
 Results: Initial therapy Pyrimethamine 200 mg was given for 6 weeks. Maintenance therapy (suppressive, secondary prophylaxis) is given for life if immune reconstitution does not occur. Primary prophylaxis against toxoplasmic encephalitis is given to patients who are seropositive for Toxoplasma.
 Conclusion: Initial therapy, maintenance, and primary prophylaxis can be useful to prevent worsening of the prognosis of toxoplasmosis disease.
 
 
 

In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii

Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii. Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii. The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC50 values of 1B (0.468–0.952 μM), 2B (0.204–0.349 μM) and 3B (0.661–1.015 μM) against T. gondii. As a measure of cytotoxicity the compounds showed a TD50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii. Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection.

Clinical and prognostic features of cerebral toxoplasmosis in HIV-infected patients in Lubumbashi, Democratic Republic of the Congo

Introduction: Cerebral toxoplasmosis is the main opportunistic infection of the central nervous system (CNS) during in human immunodeficiency virus (HIV)-infection. The purpose of this study is to describe current epidemiologic, clinical, diagnostic, and prognostic features of cerebral toxoplasmosis during HIV-infection in hospital setting in Lubumbashi. Methods: This descriptive and analytic study examined the records of 21 HIV-positive patients with cerebral toxoplasmosis. Data were collected over 36 months (from January 2015 to December 2017) at the HIV/AIDS Center of Excellence in Lubumbashi (Democratic Republic of the Congo). Results: Twenty-one patients on 4,283 followed for HIV-infection completed the diagnostic criteria (a prevalence of 0.5%) with a sex ratio (M / F) of 1.3 and a mean age of 41.0±6 years. Major clinical manifestations were fever (100%), headaches (100%), motor deficit (61.9%), intracranial hypertension (47.6%), seizures (47.6%), and disorders of consciousness (42.9%). Cerebral imaging studies (4 Computed tomography scan) were performed and showed hypodensities with peripheral enhancement by cockade in 75% of the cases. The mean CD4 T-cell counts was 180.6±161.9 cells / mm3. Co-trimoxazole was the main anti-toxoplasma drug in all cases. The lethality rate was 42.9%. Conclusion: Early detection and primary prevention in HIV-infected patients remain essential to improve the prognosis and survival of these patients.

Multicenter Comparative Assessment of the TIB MolBiol Toxoplasma gondii Detection Kit and Four Laboratory-Developed PCR Assays for Molecular Diagnosis of Toxoplasmosis

Toxoplasmosis can be a life-threatening infection, particularly during pregnancy and in immunocompromised patients. The biological diagnosis of toxoplasmosis is challenging and has been revolutionized by molecular detection methods. This article summarizes the data of a multicenter study involving four centers to assess the performances of a commercial PCR assay as compared with four in-house PCR assays using Toxoplasma gondii standards, 20 external quality control specimens, and 133 clinical samples. This clinical cohort includes well-characterized clinical samples corresponding to different clinical situations: confirmed congenital toxoplasmosis (44 samples), toxoplasmosis in immunocompromised patients (25samples), and chorioretinitis (5 samples). Furthermore, 59 samples from patients without toxoplasmosis were included as negative controls. The analytical sensitivities of the five methods tested were very similar; and the limit of Toxoplasma DNA detection was around 0.01 T. gondii genome per reaction for all the methods. The overall concordance between the commercial PCR and the four in-house PCR assays was 97.7% (130/133). The clinical sensitivity and specificity were >98% and could be increased for the commercial kit when PCR was performed in multiplicate to detect low parasitic loads. In conclusion, thecommercial PCR assay shows suitable performances to diagnose the different clinical forms of toxoplasmosis.

Congenital toxoplasmosis the overlooked disease: a case report

The causative agent of congenital toxoplasmosis (CT) is Toxoplasma gondii, an obligate intracellular parasitic protozoan presenting as a zoonotic infection distributed worldwide. Congenital toxoplasmosis may lead to abortion, intrauterine growth restriction, hepatosplenomegaly, jaundice and several neurological and ocular manifestations. The classic pathognomonic manifestations are the triad of intracranial calcifications, hydrocephalus and chorioretinitis. However, the majority of infected infants are asymptomatic at birth. Herein, we reported a case of severe CT in a late preterm newborn. Interestingly, the majority of the manifestations reported for CT were observed in this case. The high anti-toxoplasma antibodies (IgM and IgG) in the infant and his mother confirmed the diagnosis.

EVALUATION OF Toxoplasma gondii SEROPREVALENCE AND IGG AVIDITY TEST RESULTS AMONG CHILDBEARING-AGE WOMEN IN KARABUK PROVINCE

Toxoplasmosis is a zoonotic infectious disease that is common worldwide and caused by the Toxoplasma gondii. Congenital toxoplasmosis is one of the major complications of this infection. The present study aimed to investigate T.gondii seroprevalence and evaluate the IgG avidity test results among childbearing- age women retrospectively. A total of 9401 samples obtained from childbearing -age (15-49 years of age) women who attended Karabuk University Training and Research Hospital between February 2016- January 2020, over the four-year, were included in the study.The Toxoplasma-IgM, Toxoplasma-IgG antibody, and Toxoplasma IgG avidity tests were analyzed chemiluminescent method by using ARCHITECT I 2000 SR immunoassay device (Abbott Laboratories, USA). Toxoplasma-IgM and Toxoplasma-IgG seropositivity were detected as 0.7% (67/9401) and 15.7% (1415/9005) respectively. A high percentage of Toxoplasma-IgM and Toxoplasma-IgG seropositivity were detected among 31-35 years of age group. The Toxoplasma seropositivity increased by age, but no statistically difference was found (P >0.05).The Toxoplasma IgG avidity was high in 45 patients (69.4%), low avidity was detected in 16 patients (22.6%) and from the remaining 6 patients were borderline (8%). The Toxoplasma IgM and IgG seropositivity rate decreased 2016 to 2020. The highest Toxoplasma IgM and IgG seropositivity were in 2016 with 1.2% and 16.8%, respectively. The T. gondi seropositivity rate was decreased from 2016 to 2020; it is probably a result of increasing awareness of the disease among patients. We think our results will contribute to the epidemiological data in our province and country and raise awareness.

Hearing brain evaluated using near-infrared spectroscopy in congenital toxoplasmosis

Congenital toxoplasmosis (CT) is a known cause of hearing loss directly caused by Toxoplasma gondii. Hearing loss might result from sensory, neural, or sensorineural lesions. Early treated infants rarely develop hearing loss, but retinochoroidal lesions, intracranial calcifications and hydrocephalus are common. In this study, we aimed to evaluate the brain evoked hemodynamic responses of CT and healthy infants during four auditory stimuli: mother infant directed speech, researcher infant directed speech, mother reading and researcher recorded. Children underwent Transitionally Evoked Otoacoustic Emission Auditory Testing and Automated Brainstem Auditory Response tests with normal auditory results, but with a tendency for greater latencies in the CT group compared to the control group. We assessed brain hemodynamics with functional near-infrared spectroscopy (fNIRS) measurements from 61 infants, and we present fNIRS results as frequency maps of activation and deactivation for each stimulus. By evaluating infants in the three first months of life, we observed an individual heterogeneous brain activation pattern in response to all auditory stimuli for both groups. Each channel was activated or deactivated in less than 30% of children for all stimuli. There is a need of prospective studies to evaluate if the neurologic or auditory changes course with compromise of children outcomes.

Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis.

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).

Evaluation of implementation of the primary, secondary and tertiary prevention measures of the Surveillance Program of Gestational and Congenital Toxoplasmosis in the city of Londrina-PR.

Toxoplasmosis acquired during pregnancy is one that can lead to death or malformations of the foetus, and it is a complex disease to diagnose. The objective of the study was to evaluate the Surveillance Program of Gestational and Congenital Toxoplasmosis. To assess primary prevention, 424 pregnant women were interviewed regarding their knowledge of prevention measures in 2019. Secondary prevention measures were assessed, and the results of anti-Toxoplasma gondii serological tests were collected from pregnant women, from 2015 to 2018. In tertiary prevention measures, babies of mothers with a recent suspicion of T. gondii infection were screened to verify forwarding to the reference service. As a result, 45.5% (192/424) reported that they had received guidance from health professionals; 35.4% (68/192) changed their risk habits. The variables of schooling and age, having received prior guidance from health professionals and feline possession, proved to be significant when associated with the notions of preventive measures. 90.2% (17,423/19,319) of pregnant women had undergone serological tests to detect anti-T. gondii antibodies, but there was an excess in requests for tests and medication and only 40.6% (26/64) of the children were referred to the reference hospital. The Program presents positive results about the performance of serological screening in prenatal care; however, the dissemination of knowledge as for the prevention of toxoplasmosis and the request for tests need to be improved.

Insights into immunopathology and triggering of apoptosis in chronic cerebral toxoplasmosis using murine models.

toxoplasmosis is a cosmopolitan protozoan disease with a wide range of neuropathology. Recent studies identified its potential association with several mental disorders e.g. schizophrenia dependable on apoptosis in their pathogenesis. We investigated value of toxoplasmosis to induce apoptosis of the neuronal cells. per-orally infected C57BL/6 mice with 15-20 cysts of the avirulent T. gondii Beverly strain at 9-11 weeks of age were examined 12 weeks later during parasite establishment. Distributions of the parasite's cysts and the histopathological lesions in the brains were analyzed using Image J software. Relative expression of TNF-α and iNOS of cell-mediated immunity (CMI), Bax (pro-apoptosis) and Bcl-2 (anti-apoptosis) were all assessed using immunohistochemistry. higher parasite burden was seen in the forebrain with p value <= 0.05. Dramatically increased TNF-α, iNOS, and Bax expressions with Bax/Bcl-2 ratio 2.42:0.52 were reported (p value <= 0.05). The significant correlation between Bax data and different CMI biomarkers including TNF-α and i-NOS was evaluated. Interestingly, no significant correlation was seen between TNF-α, iNOS, Bax and Bcl-2 expressions and location of the parasite. However, Bax/Bcl-2 ratio was statistically correlated with CMI biomarkers and whole sample mean parasite burden, p value <= 0.05. Chronic toxoplasmosis exhibits an immense pro-apoptotic signal on the cerebral tissues of experimental mice.

A Family of Toxoplasma gondii Genes Related to GRA12 Regulate Cyst Burdens and Cyst Reactivation.

ABSTRACTToxoplasma gondii causes a chronic infection that renders the immunocompromised human host susceptible to toxoplasmic encephalitis triggered by cyst reactivation in the central nervous system. The dense granule protein GRA12 is a major parasite virulence factor required for parasite survival during acute infection. Here, we characterized the role of four GRA12-related genes in acute and chronic stages of infection. While GRA12A, GRA12B, and GRA12D were highly expressed in asexual stage tachyzoites and bradyzoites, expression of GRA12C appeared to be restricted to the sexual stages. In contrast to deletion of GRA12 (Δgra12), no major defects in acute virulence were observed in Δgra12A, Δgra12B, or Δgra12D parasites, though Δgra12B parasites exhibited an increased tachyzoite replication rate. Bradyzoites secreted GRA12A, GRA12B, and GRA12D and incorporated these molecules into the developing cyst wall, as well as the cyst matrix in distinct patterns. Similar to GRA12, GRA12A, GRA12B, and GRA12D colocalized with the dense granules in extracellular tachyzoites, with GRA2 and the intravacuolar network in the tachyzoite stage parasitophorous vacuole and with GRA2 in the cyst matrix and cyst wall. Chronic stage cyst burdens were decreased in mice infected with Δgra12A parasites and were increased in mice infected with Δgra12B parasites. However, Δgra12B cysts were not efficiently maintained in vivo. Δgra12A, Δgra12B, and Δgra12D in vitro cysts displayed a reduced reactivation efficiency, and reactivation of Δgra12A cysts was delayed. Collectively, our results suggest that a family of genes related to GRA12 play significant roles in the formation, maintenance, and reactivation of chronic stage cysts.IMPORTANCE If host immunity weakens, Toxoplasma gondii cysts recrudesce in the central nervous system and cause a severe toxoplasmic encephalitis. Current therapies target acute stage infection but do not eliminate chronic cysts. Parasite molecules that mediate the development and persistence of chronic infection are poorly characterized. Dense granule (GRA) proteins such as GRA12 are key virulence factors during acute infection. Here, we investigated four GRA12-related genes. GRA12-related genes were not major virulence factors during acute infection. Instead, GRA12-related proteins localized at the cyst wall and cyst matrix and played significant roles in cyst development, persistence, and reactivation during chronic infection. Similar to GRA12, the GRA12-related proteins selectively associated with the intravacuolar network of membranes inside the vacuole. Collectively, our results support the hypothesis that GRA12 proteins associated with the intravacuolar membrane system support parasite virulence during acute infection and cyst development, persistence, and reactivation during chronic infection.

The Immunoproteasome Subunits LMP2, LMP7 and MECL-1 Are Crucial Along the Induction of Cerebral Toxoplasmosis.

Cell survival and function critically relies on the fine-tuned balance of protein synthesis and degradation. In the steady state, the standard proteasome is sufficient to maintain this proteostasis. However, upon inflammation, the sharp increase in protein production requires additional mechanisms to limit protein-associated cellular stress. Under inflammatory conditions and the release of interferons, the immunoproteasome (IP) is induced to support protein processing and recycling. In antigen-presenting cells constitutively expressing IPs, inflammation-related mechanisms contribute to the formation of MHC class I/II-peptide complexes, which are required for the induction of T cell responses. The control of Toxoplasma gondii infection relies on Interferon-γ (IFNγ)-related T cell responses. Whether and how the IP affects the course of anti-parasitic T cell responses along the infection as well as inflammation of the central nervous system is still unknown. To answer this question we used triple knockout (TKO) mice lacking the 3 catalytic subunits of the immunoproteasome (β1i/LMP2, β2i/MECL-1 and β5i/LMP7). Here we show that the numbers of dendritic cells, monocytes and CD8+ T cells were reduced in Toxoplasma gondii-infected TKO mice. Furthermore, impaired IFNγ, TNF and iNOS production was accompanied by dysregulated chemokine expression and altered immune cell recruitment to the brain. T cell differentiation was altered, apoptosis rates of microglia and monocytes were elevated and STAT3 downstream signaling was diminished. Consequently, anti-parasitic immune responses were impaired in TKO mice leading to elevated T. gondii burden and prolonged neuroinflammation. In summary we provide evidence for a critical role of the IP subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 for the control of cerebral Toxoplasma gondii infection and subsequent neuroinflammation.

Development of a Method for Identification and Quantification of Sulfadiazine and Pyrimethamine in Serum of Congenital Toxoplasmosis Patients

Infection with Toxoplasma gondii, is one of the most widespread zoonoses in the world. Congenital toxoplasmosis (CT) is particularly risky due to its fetal complications...

Evaluation of Knowledge of Students of the Lorestan University of Medical Sciences about Congenital Toxoplasmosis

Background: Toxoplasmosis is the most important parasitic infection associated with central nervous system. Sufficient knowledge and information about congenital toxoplasmosis and its effective factors is very helpful for health graduates in the prevention, early diagnosis, and treatment of the disease in infants. This study aimed to investigate the knowledge level of senior students related to pregnant women in Lorestan University of Medical Sciences, Khorramabad, Iran, about congenital toxoplasmosis. Materials and Methods: This study included 177 students who would deal with pregnant women in their future careers. The students' knowledge and information about congenital toxoplasmosis were assessed and measured based on a pre-designed questionnaire. The Mann-Whitney and Chi-square tests were used to compare the obtained data. Results: The results of this study showed that the students' knowledge about congenital toxoplasmosis was not in a desired range (4.72±71.14%). Based on the results, the level of knowledge was significantly lower in nursing and nutrition students (P=0.013), younger age groups (P=0.013), dormitory residents (P=0.002), and undergraduates (P&lt;0.001), compared to other students (P&lt;0.05). Conclusion: The results of the present study indicated the poor level of information of senior students related to pregnant women about congenital toxoplasmosis. Emphasis is placed on the importance of the disease and its irreparable damage to the fetus, development of plans to increase students' awareness of the disease, as well as ways of transmission and prevention.