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1.
Mem Inst Oswaldo Cruz ; 116: e200417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33729328

RESUMO

BACKGROUND: Toxoplasma gondii causes toxoplasmosis and is controlled by activated macrophages. However, infection of macrophages by tachyzoites induces TGF-ß signaling (TGF-s) inhibiting nitric oxide (NO) production. NO inhibition may be a general escape mechanism of distinct T. gondii strains. OBJECTIVES: To evaluate in activated macrophages the capacity of T. gondii strains of different virulence and genetics (RH, type I; ME-49, type II; VEG, type III; P-Br, recombinant) to evade the NO microbicidal defense system and determine LC3 loading to the parasitophorous vacuole. METHODS: Activated peritoneal macrophages were infected with the different T. gondii strains, NO-production was evaluated by the Griess reagent, and inducible nitric oxide synthase expression, TGF-s, and LC3 localisation assayed by immunofluorescence. FINDINGS: Only RH persisted in macrophages, while VEG was more resistant than P-Br and ME-49. All strains induced TGF-s, degradation of inducible nitric oxide synthase, and NO-production inhibition from 2 to 24 h of infection, but only RH sustained these alterations for 48 h. By 24 h of infection, TGF-s lowered in macrophages infected by ME-49, and P-Br, and NO-production recovered, while VEG sustained TGF-s and NO-production inhibition longer. LC3 loading to parasitophorous vacuole was strain-dependent: higher for ME-49, P-Br and VEG, lower for RH. All strains inhibited NO-production, but only RH sustained this effect probably because it persisted in macrophages due to additional evasive mechanisms as lower LC3 loading to parasitophorous vacuole. MAIN CONCLUSIONS: These results support that T. gondii can escape the NO microbicidal defense system at the initial phase of the infection, but only the virulent strain sustain this evasion mechanism.


Assuntos
Macrófagos Peritoneais/parasitologia , Macrófagos/parasitologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/biossíntese , Toxoplasma/fisiologia , Animais , Macrófagos/metabolismo , Camundongos , Toxoplasmose Animal/parasitologia
2.
Rev Bras Parasitol Vet ; 30(1): e017520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533795

RESUMO

We investigated the occurrence of Toxoplasma gondii and Neospora caninum antibodies in pigs raised in the Northeast of Pará, Brazil. At Study I, convenience sampled 151 pigs at two slaughterhouses, with and without state inspection; and Study II, which assessed 159 pigs with probabilistic sampling from nine pig farms. Serological analysis was performed using indirect fluorescent antibody test for T. gondii and N. caninum with a cutoff of 64 and 50, respectively. Overall, 6.77% pigs were seropositive for T. gondii and 5.16% for N. caninum. In Study I, pigs slaughtered with and without state inspection presented similar occurrence for both coccidia (p>0.05). Study II found an association between N. caninum seropositivity and sludge discarded into the soil, feeding pigs with animal-based protein, subsistence system, and absence of nipple drinkers. No association was found for T. gondii. Pigs from Pará are a potential source of T. gondii infection to humans. To our best knowledge, this is the first study to report anti-N. caninum antibodies in the serum of pigs in Pará State, Brazilian Amazon.


Assuntos
Coccidiose , Neospora , Doenças dos Suínos , Toxoplasma , Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Coccidiose/epidemiologia , Coccidiose/imunologia , Coccidiose/veterinária , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Neospora/imunologia , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia
3.
Rev Bras Parasitol Vet ; 30(1): e028520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605391

RESUMO

This study aimed to identify members of the Sarcocystidae family in naturally infected wild birds at a rescue center in the state of Minas Gerais, southeastern Brazil. The heart and brain of 44 wild birds were evaluated by bioassay in mice to detect T. gondii, and extracted DNA was used for nested PCR of the 18S ribosomal DNA gene to detect members of the Sarcocystidae family. The positive samples were sequenced, assembled, edited and compared with sequences deposited in GenBank. Toxoplasma gondii was isolated from six (13.6%) out of 44 birds. Toxoplasma gondii DNA was identified in 10/44 (22.7%) of the birds. The amplified sequences exhibited 100% similarity with the DNA of the ME49 strain of T. gondii. Sarcocystis DNA (99% similarity) was identified in 5/44 (11.4%) of the birds. T. gondii and Sarcocystis spp. are common in wild birds in Minas Gerais, Brazil.


Assuntos
Doenças das Aves , Coccidiose , Sarcocystidae , Animais , Bioensaio , Doenças das Aves/epidemiologia , Doenças das Aves/parasitologia , Aves , Brasil , Coccidiose/epidemiologia , DNA de Protozoário , Camundongos , Reação em Cadeia da Polimerase , RNA Ribossômico 18S/genética , Sarcocystidae/genética , Sarcocystis/genética , Toxoplasma/genética , Toxoplasmose Animal/epidemiologia
4.
BMC Infect Dis ; 21(1): 188, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602170

RESUMO

BACKGROUND: Toxoplasma gondii is a protozoan parasite that infects cats as definitive hosts and other warm-blooded animals including humans as intermediate hosts. It forms infectious cysts in the brain, muscle and other tissues establishing life-long latent infection. Approximately 10% of the US population is infected. While latent infections are largely asymptomatic, they are associated with neurological deficits and elevated risks of neuropsychiatric diseases. METHODS: This cross-sectional epidemiological study investigated associations of T. gondii infections with biomarkers of inflammation and vascular injury: soluble intercellular adhesion molecule 1 (ICAM-1), soluble vascular cell adhesion molecule 1 (VCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Serum samples from 694 adults in the Raleigh-Durham-Chapel Hill, North Carolina metropolitan area were tested for IgG antibody response to T. gondii, and for the above biomarkers using commercially available assays. RESULTS: T. gondii seroprevalence rate in this sample was 9.7%. Seropositivity was significantly associated with 11% (95% confidence limits 4, 20%) greater median levels of VCAM-1 (p = 0.003), and marginally significantly with 9% (1, 17%), and 36% (1, 83%) greater median levels of ICAM-1, and CRP, respectively (p = 0.04 for each) after adjusting for sociodemographic and behavioral covariates, while the 23% (- 7, 64%) adjusted effect on SAA was not statistically significant (p = 0.15). CONCLUSIONS: Latent infections with T. gondii are associated with elevated biomarkers of chronic inflammation and vascular injury that are also known to be affected by ambient air pollution.


Assuntos
Inflamação/sangue , Toxoplasmose/sangue , Lesões do Sistema Vascular/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antiprotozoários/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Adulto Jovem
5.
Parasite ; 28: 13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33629951

RESUMO

The surface protein TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain) has been characterized as an important regulator of cell-mediated immune responses in various infections. However, TIGIT expression in immune cells of mice infected with Toxoplasma gondii has not been investigated. Here, we detected TIGIT expression and related phenotypes by flow cytometry and real-time PCR in splenic and circulatory T cells of mice infected with the T. gondii RH strain. We found that the expression of TIGIT on the surface of CD4+ T cells and CD8+ T cells from the spleen and peripheral blood mononuclear cells decreased in the early stage, but increased significantly in the late stage of acute T. gondii infection in mice. Importantly, TIGIT expression was positively correlated with lesions in the murine spleen. In addition, T. gondii-specific TIGIT+TCM cells in the spleen were activated and transformed into TIGIT+ TEM cells. Hematoxylin and eosin staining of spleen sections and real-time PCR showed that the severity of splenic lesions was positively correlated with the T. gondii load. This study demonstrates that acute T. gondii infection can regulate the expression of TIGIT in T cells and affect immune cell function.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Receptores Imunológicos/genética , Toxoplasmose/imunologia , Animais , Leucócitos Mononucleares/imunologia , Camundongos , Baço/citologia , Toxoplasma
6.
Ecotoxicol Environ Saf ; 213: 112048, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33610941

RESUMO

We conducted a large-scale epidemiological investigation to detect the prevalence of Toxoplasma gondii in four marine bivalve shellfish species collected from six representative coastal regions of Weihai, eastern China. Between January 2018 and December 2018, 14,535 marine bivalve shellfish pooled into 2907 samples were randomly collected and examined for T. gondii DNA by a nested PCR assay targeting B1 gene. The results showed that 2.8% (82) of the 2907 pooled samples were tested positive for T. gondii DNA. Two T. gondii genotype (ToxoDB Genotype #9 and ToxoDB Genotype #1) were identified PCR-restriction fragment length polymorphism analysis. Factors that were found significantly associated with the presence of T. gondii DNA in marine bivalve shellfish included the source of samples (being wild) (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.00-5.84; p < 0.01), surface runoff near the sampling site (OR, 2.64; 95% CI, 1.47-4.72; p < 0.01), and presence of cats near the sampling site (OR, 1.77; 95% CI, 1.02-3.07; p = 0.04). Moreover, the prevalence of T. gondii DNA in marine bivalve shellfish correlated with temperature (Pearson's correlation: R = 0.75, p = 0.0049) and precipitation (R = 0.87, p = 0.00021). These findings provide new insights into the presence of T. gondii DNA in marine bivalve shellfish and highlight the impact of human activity on marine pollution by such an important terrestrial pathogen pollutant.


Assuntos
Bivalves/parasitologia , Toxoplasmose Animal/epidemiologia , Animais , Bivalves/genética , China/epidemiologia , Genótipo , Humanos , Reação em Cadeia da Polimerase/métodos , Prevalência , Fatores de Risco , Frutos do Mar , Toxoplasma/genética
7.
Nat Commun ; 12(1): 120, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402698

RESUMO

Mitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit-a. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF1. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa.


Assuntos
Mitocôndrias/ultraestrutura , Membranas Mitocondriais/ultraestrutura , ATPases Mitocondriais Próton-Translocadoras/química , Subunidades Proteicas/química , Proteínas de Protozoários/química , Toxoplasma/ultraestrutura , Sítios de Ligação , Cardiolipinas/química , Cardiolipinas/metabolismo , Microscopia Crioeletrônica , Expressão Gênica , Mitocôndrias/genética , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Modelos Moleculares , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas/química , Proteínas/genética , Proteínas/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Especificidade por Substrato , Termodinâmica , Toxoplasma/genética , Toxoplasma/metabolismo
8.
Trop Anim Health Prod ; 53(1): 76, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404940

RESUMO

The aim of the present study was to evaluate the spatial distribution of the prevalence of T. gondii in cows using the indirect immunofluorescence assay and determine associated risk factors. Serum samples were collected from 2970 cows on 263 rural farms in 223 municipalities. A questionnaire was administered to herd owners to collect data for the evaluation of risk factors associated with this disease. Mean seroprevalence of T. gondii in cows was 8.48% (95% CI: 7.48 to 9.49). The microregions with the greatest likelihood (p ≤ 0.05) of having infected animals were Anápolis, Ceres, São Miguel do Araguaia, the Federal District, Anicuns, and Vão do Paraná. The purchase of females or males for reproductive/breeding purposes was significantly associated (p ≤ 0.05) with the prevalence of T. gondii in these regions. A positive correlation (0.7618; p = 0.047) was found between the prevalence of T. gondii and total area in hectares of forests in these regions, suggesting that wild cats may be disseminating T. gondii at these sites. The present results highlight the importance of considering the meat from these animals to be an important infection route for humans who eat raw or undercooked food.


Assuntos
Doenças dos Bovinos/epidemiologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/epidemiologia , Animais , Brasil/epidemiologia , Bovinos , Doenças dos Bovinos/parasitologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasmose Animal/parasitologia
9.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466510

RESUMO

Ca2+ signaling has been involved in controling critical cellular functions such as activation of proteases, cell death, and cell cycle control. The endoplasmatic reticulum plays a significant role in Ca2+ storage inside the cell, but mitochondria have long been recognized as a fundamental Ca2+ pool. Protozoan parasites such as Plasmodium falciparum, Toxoplasma gondii, and Trypanosoma cruzi display a Ca2+ signaling toolkit with similarities to higher eukaryotes, including the participation of mitochondria in Ca2+-dependent signaling events. This review summarizes the most recent knowledge in mitochondrial Ca2+ signaling in protozoan parasites, focusing on the mechanism involved in mitochondrial Ca2+ uptake by pathogenic protists.


Assuntos
Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Mitocôndrias/metabolismo , Parasitos/metabolismo , Animais , Eucariotos/metabolismo , Humanos , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Trypanosoma cruzi/metabolismo
10.
Int J Food Microbiol ; 341: 109031, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33485138

RESUMO

Toxoplasmosis is an infection caused by the protozoan parasite, Toxoplasma gondii. It has been reported as the fourth leading cause of hospitalization and second leading cause of death among 31 major foodborne pathogens in the United States. Humans are infected through consumption of raw or undercooked meat containing T. gondii tissue cysts or ingestion of food, soil, or water contaminated by T. gondii oocysts. People often lack knowledge about how to prevent T. gondii infection, especially the risks associated with eating or handling raw or undercooked meat. Current available data on cooking or low temperature storage for whole cuts of meat are not sufficient to validate inactivation of T. gondii. The objectives of the present study were to estimate the relationship of time and temperature with the survival rate of T. gondii during cooking and low temperature storage of fresh cut meats. We used different statistical sampling techniques such as bootstrap resampling and Gibbs sampling to establish those relationships. Monte Carlo simulation was used to estimate the safe temperature for cooking and storing meats. The results showed no detection of T. gondii in fresh meats when the internal temperature reached above 64 °C (147.2 °F) and below -18 °C (0 °F). The tissue cysts can remain viable at least up to 30 days at 4 °C (39 °F) and about 3.3% cysts survived at 62.8 °C (145 °F). This study can provide helpful information in improving the risk models to further mitigate the public health burden of toxoplasmosis.


Assuntos
Temperatura Baixa , Doenças Transmitidas por Alimentos/prevenção & controle , Temperatura Alta , Carne/parasitologia , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose/prevenção & controle , Culinária , Doenças Transmitidas por Alimentos/parasitologia , Humanos , Alimentos Crus/parasitologia , Taxa de Sobrevida , Toxoplasmose/parasitologia
11.
Parasitol Res ; 120(2): 763-767, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415403

RESUMO

Toxoplasmosis is the most prevalent zoonosis in the world and is associated with a large spectrum of diseases. Acute acquired toxoplasmosis (AAT) is considered a benign and self-limiting disease but severe postnatal infections have been reported, particularly in South America. Laboratory diagnosis is based on the detection of anti-Toxoplasma gondii IgM, IgG, and presence of low IgG avidity. However, these assays present limitations, and therefore, PCR has been suggested as an alternative diagnostic tool. In this study, we performed real-time and nested PCR in DNA blood samples from 59 individuals with AAT lasting less than 80 days. None of the patients had parasitic DNA detected by PCR, even in the more severe cases or when blood was collected early after disease onset. These negative results indicate that the parasitemia kinetics needs investigation to determine the best time for blood sampling, especially in immunocompetent individuals. Thus, we emphasize that a negative PCR result does not exclude recent T. gondii infection, and serological criteria are still decisive for the laboratory diagnosis of AAT.


Assuntos
Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase , Toxoplasma/isolamento & purificação , Toxoplasmose/diagnóstico , Doença Aguda , Adolescente , Adulto , Criança , DNA de Protozoário/sangue , DNA de Protozoário/genética , Feminino , Humanos , Pessoa de Meia-Idade , Resultados Negativos , Toxoplasma/genética , Toxoplasmose/sangue , Toxoplasmose/parasitologia , Adulto Jovem
12.
Parasitol Res ; 120(2): 665-677, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415402

RESUMO

This study aimed to genetically characterize Toxoplasma gondii isolates obtained from free-range chickens reared in the metropolitan region of the state of Rio de Janeiro, Brazil, and to evaluate the morbidity and histological changes associated with these isolates in mice. A mouse bioassay was used to isolate T. gondii from a pool of tissue samples (brain, heart, and thigh muscles) collected from 163 chickens. The 36 isolates obtained were genetically characterized by restriction fragment polymorphism (PCR-RFLP) analysis of the SAG1, 5'-3'SAG2, aSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico, and CS3 genomic regions. Seventeen atypical genotypes were identified and nine of them were reported for the first time. All identified genotypes caused clinical signs and histological changes in mice, with the majority being associated with high cumulative morbidity (65%) and severe or very severe histological changes (76%). The exclusive identification of atypical genotypes, with a predominance of new genotypes, indicates great genetic diversity of T. gondii in the region studied. In addition, the finding that all identified genotypes caused clinical signs and often severe histological changes in mice suggests potentially relevant virulence of these strains.


Assuntos
Galinhas/parasitologia , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Animais , Brasil/epidemiologia , Genótipo , Camundongos , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/epidemiologia , Virulência/genética
13.
Parasitol Res ; 120(2): 755-761, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33447884

RESUMO

Toxoplasma gondii infection was one of the most frequent AIDS-defining conditions in HIV-infected individuals until the advent of combination antiretroviral therapy. We aimed to assess the clinical load, coinfection, and mortality, as well as time trends for people living with HIV and hospitalized with Toxoplasma gondii infection, in Spain from 1997 to 2015. Retrospective observational analysis using the Spanish National Registry of Hospital Discharges. Information was retrieved for the study period using the International Classification of Diseases, 9th revision. There were 66,451,094 hospital admissions in Spain from 1997 to 2015, including 472,269 (0.71%) in people living with HIV. Toxoplasma gondii infection was registered in 9006 of these (overall prevalence 1.91%), making it the fifth most common opportunistic infection in hospitalized HIV-positive patients. Prevalence of Toxoplasma gondii infection declined in this group from 4.2% in 1997 to 0.8% in 2015 (p < 0.001), while mean age increased, from 35 years in 1997 to 44 years in 2015. The overall in-hospital mortality rate declined from 13.5% in 1997 to 8.9% in 2015, and it was higher in the concomitant presence of bacterial pneumonia (28.9% vs. 10.2%, p < 0.001), cryptosporidiosis (26.9% vs. 11.5%; p = 0.03), cytomegalovirus disease (18.2% vs. 11.2%, p < 0.001), Pneumocystis jiroveci pneumonia (31.5% vs. 10.5%, p < 0.001), leukoencephalopathy (19.8% vs. 11.78% p < 0.001), and wasting syndrome (29.3% vs 10.9%; p < 0.001). Toxoplasma gondii infection prevalence has significantly declined among hospitalized HIV-infected patients in Spain during the last two decades, coinciding with the widespread use of combination antiretroviral therapy.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Hospitalização/estatística & dados numéricos , Toxoplasmose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Humanos , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Toxoplasma/isolamento & purificação , Toxoplasmose/microbiologia , Toxoplasmose/parasitologia
14.
Sheng Wu Gong Cheng Xue Bao ; 37(1): 290-300, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33501809

RESUMO

For improving epitope immunogenicity and achieving the co-immunization, late protein 1 (L1) of HPV type 16 (HPV16L1) was selected as the vector to carry the dominant epitope of Toxoplasma gondii because of the shared common population between Toxoplasma gondii and human papillomavirus (HPV). RSepitope-HPV16L1 (RSepitope fused at the "N-terminus" of HPV16L1) and HPV16L1-RSepitope (RSepitope fused at the "C-terminus" of HPV16L1) chimeras were constructed. After transfection of COS-7 cells with the recombinants, Western blot, RT-PCR, and immunofluorescence experiments confirmed that RSepitope-HPV16L1 could successfully express the corresponding mRNA and protein of RSepitope and HPV16L1, but the HPV16L1-RSepitope construct could not. A "prime-boost" immunization program was applied in mice to further evaluate the immune response elicited by the constructs, and the RSepitope-HPV16L1 immunization group produced the most significantly increased humoral and cellular immune responses (the highest RSepitope-specific IgG antibody level and the highest IFN-γ production, respectively), in which both elevated Th1 and Th2 immune responses were obtained. Moreover, the advantage of HPV16L1 as an epitope carrier was remarkable for RSepitope-HPV16L1, which induced a more prominent immunological response than RSepitope alone (without fusion with HPV16L1). Our research indicated that the N-terminus of HPV16L1 could be a better insertion site for enhancing target epitope immunogenicity, and our study offers a design for epitope vaccine of reasonable combination.


Assuntos
Toxoplasma , Vacinas de DNA , Animais , Formação de Anticorpos , Epitopos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Vacinação
15.
Nat Commun ; 12(1): 116, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414462

RESUMO

Apicomplexan parasites have evolved efficient and distinctive strategies for intracellular replication where the timing of emergence of the daughter cells (budding) is a decisive element. However, the molecular mechanisms that provide the proper timing of parasite budding remain unknown. Using Toxoplasma gondii as a model Apicomplexan, we identified a master regulator that controls the timing of the budding process. We show that an ApiAP2 transcription factor, TgAP2IX-5, controls cell cycle events downstream of centrosome duplication. TgAP2IX-5 binds to the promoter of hundreds of genes and controls the activation of the budding-specific cell cycle expression program. TgAP2IX-5 regulates the expression of specific transcription factors that are necessary for the completion of the budding cycle. Moreover, TgAP2IX-5 acts as a limiting factor that ensures that asexual proliferation continues by promoting the inhibition of the differentiation pathway. Therefore, TgAP2IX-5 is a master regulator that controls both cell cycle and developmental pathways.


Assuntos
Ciclo Celular/fisiologia , Divisão Celular/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Toxoplasma/genética , Toxoplasma/fisiologia , Proliferação de Células , Centrossomo , Replicação do DNA , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Organismos Geneticamente Modificados , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
J Environ Manage ; 278(Pt 1): 111513, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33113398

RESUMO

Nowadays, it is necessary to improve the efficiency of wastewater treatment plant treatments. In this context the use of biofilter species, like Dreissena polymorpha, as a bioremediation tool in wastewater is increasingly highlighted. The innovative aim of this study is to evaluate the zebra mussel survival in the outlet channel of a conventional WWTP to use them as bioremediation tool. For this, mussels were transplanted in the outlet channel for 28 days and different biomarkers were monitored. D. polymorpha is able to maintain itself in good physiological conditions until 21 days, yet at 28 days a high mortality rate (24%), a decrease in filtration efficiency (8/15 mussels filtered and 17.0% of filtration rate) and antioxidant system activation (CAT activity et gpx gene expression increase) suggest an exhaustion. Some biomarkers suggested a hypoxic stress. Despite the unfavourable conditions, bivalves have bioaccumulated pathogenic protozoa (Toxoplasma gondii and Giardia duodenalis) during the exposure. Zebra mussel seems to be a promising tool for bioremediation in wastewater.


Assuntos
Bivalves , Dreissena , Toxoplasma , Animais , Biodegradação Ambiental , Águas Residuárias
17.
PLoS Negl Trop Dis ; 14(12): e0008944, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33320848

RESUMO

BACKGROUND: Toxoplasma gondii is an obligate intracellular and neurotropic apicomplexan protozoan parasite infecting almost all warm-blooded vertebrates including humans. To date in Ethiopia, no systematic study has been investigated on the overall effects of potential risk factors associated with seropositivity for Toxoplasma gondii among pregnant women and HIV infected individuals. We intended to determine the potential risk factors (PRFs) associated with seropositivity for Toxoplasma gondii from published data among pregnant women and HIV infected individuals of Ethiopia. METHODOLOGY: An systematic review of the previous reports was made. We searched PubMed, Science Direct, African Journals Online, and Google Scholar for studies with no restriction on the year of publication. All references were screened independently in duplicate and were included if they presented data on at least two risk factors. Meta-analysis using the random or fixed-effects model was made to calculate the overall effects for each exposure. RESULTS: Of the 216 records identified, twenty-four reports met our eligibility criteria, with a total of 6003 individuals (4356 pregnant women and 1647 HIV infected individuals). The pooled prevalences of anti-Toxoplasma gondii antibodies were found at 72.5% (95% CI: 58.7% - 83.1%) in pregnant women and 85.7% (95% CI: 76.3% - 91.8%) in HIV infected individuals. A significant overall effect of anti-Toxoplasma gondii seropositivity among pregnant women (p < 0.05) was witnessed with age, abortion history, contact with cats, cat ownership, having knowledge about toxoplasmosis, being a housewife and having unsafe water source. Age, cat ownership, and raw meat consumption were also shown a significant effect (p < 0.05) to anti-Toxoplasma gondii seropositivity among HIV infected individuals. CONCLUSIONS: This review showed gaps and drawbacks in the earlier studies that are useful to keep in mind to design accurate investigations in the future. The pooled prevalence of anti-Toxoplasma gondii antibodies was found to be higher among pregnant women and HIV infected individuals. This suggests that thousands of immunocompromised individuals (pregnant women and HIV infected patients) are at risk of toxoplasmosis due to the sociocultural and living standards of the communities of Ethiopia. Appropriate preventive measures are needed to reduce the exposure to Toxoplasma gondii infection. Further studies to investigate important risk factors are recommended to support the development of more cost-effective preventive strategies.


Assuntos
Anticorpos Antiprotozoários/imunologia , Infecções por HIV/complicações , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Estudos Transversais , Infecções por HIV/virologia , Humanos , Hospedeiro Imunocomprometido , Gestantes , Prevalência , Fatores de Risco , Toxoplasmose/parasitologia
18.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(6): 635-639, 2020 Jul 29.
Artigo em Chinês | MEDLINE | ID: mdl-33325201

RESUMO

OBJECTIVE: To understand the prevalence and risk factors of Toxoplasma gondii infections among high-risk populations in Changzhou City, so as to provide the scientific basis for formulating effective control measures of toxoplasmosis. METHODS: Four types of high-risk populations living in Changzhou City were recruited from 2016 to 2018 as the study subjects, including HIV/AIDS patients, cancer patients, pregnant women and livestock and poultry breeding or processing workers. Each subject was investigated for the knowledge on knowledge, attitude and practice of toxoplasmosis prevention and control. In addition, serum specific IgG and IgM antibodies against T. gondii were detected, and the risk factors of T. gondii infections were identified. RESULTS: A total of 900 participants at high risk of T. gondii infections were investigated in Changzhou City from 2016 to 2018, including 150 HIV/AIDS patients, 250 cancer patients, 250 pregnant women and 250 livestock and poultry breeding or processing workers. The overall awareness rate of toxoplasmosis prevention and control knowledge was 16.8% (151/900), and the awareness rate was significantly greater in women than in men (χ2 = 41.34, P < 0.05). The awareness rate of toxoplasmosis prevention and control reduced with ages (χ2 = 147.78, P < 0.05), and increased with the education level (χ2 = 166.42, P < 0.05). In ad dition, there was an occupation-specific awareness rate of toxoplasmosis prevention and control (χ2 = 92.26, P < 0.05), and the highest awareness rate was seen in cadres and staff (47.2%, 34/72). Among all high-risk populations, 34.6% (311/900) had fre- quent contacts with cats/dogs, 40.4% (364/900) raised cats/dogs at home, 0.9% (8/900) ate raw meat, and 15.8% (142/900) sepa- rated chopping boards for raw and cooked food. Among the participants aware of toxoplasmosis prevention and control knowledge, 24.5% (37/151) contacted cats/dogs frequently, which was significantly lower than those not aware of toxoplasmosis prevention and control knowledge (36.6%, 274/749) (χ2 = 8.11, P < 0.05), and 35.1% (53/151) separated chopping boards for raw and cooked food, which was significantly higher than those not aware of toxoplasmosis prevention and control knowledge (11.9%, 89/749) (χ2 = 50.97, P < 0.05). The overall seroprevalence of T. gondii infections was 11.0% (99/900), and the positive rates of IgG antibodies against T. gondii were 6.0%, 13.9%, 4.8% and 17.3% in HIV/AIDS patients, livestock and poultry breeding or processing workers, pregnant women and cancer patients, respectively (χ2 = 25.87, P < 0.05). A higher seroprevalence of T. gon- dii infection was seen in men than in women (χ2 = 8.88, P < 0.05), and the seroprevalence increased with ages (χ2 = 37.03, P < 0.05) and reduced with education levels (χ2 = 25.07, P < 0.05). There was an occupation-specific seroprevalence of T. gondii in- fection (χ2 = 22.09, P < 0.05), and the highest seroprevalence was detected in peasants (57/330, 17.3%). CONCLUSIONS: The awareness of toxoplasmosis prevention and control knowledge is low among high-risk populations in Changzhou City. Health edu- cation pertaining to toxoplasmosis prevention and control requires to be strengthened in cancer patients and livestock and poultry breeding or processing workers who have a high seroprevalence of T. gondii infections, so as to change the poor behavior styles.


Assuntos
Anticorpos Antiprotozoários/sangue , Estudos Soroepidemiológicos , Toxoplasmose , Animais , Gatos , China , Cidades , Cães , Fazendeiros , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Gravidez , Fatores de Risco , Toxoplasma , Toxoplasmose/epidemiologia , Toxoplasmose/prevenção & controle
19.
PLoS Negl Trop Dis ; 14(12): e0008905, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382688

RESUMO

Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes.


Assuntos
Oftalmopatias/fisiopatologia , Oftalmopatias/parasitologia , Toxoplasmose/fisiopatologia , Olho/parasitologia , Olho/fisiopatologia , Oftalmopatias/imunologia , Humanos , Toxoplasma/fisiologia , Toxoplasmose/imunologia
20.
PLoS Pathog ; 16(12): e1009067, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33383579

RESUMO

Inorganic ions such as phosphate, are essential nutrients required for a broad spectrum of cellular functions and regulation. During infection, pathogens must obtain inorganic phosphate (Pi) from the host. Despite the essentiality of phosphate for all forms of life, how the intracellular parasite Toxoplasma gondii acquires Pi from the host cell is still unknown. In this study, we demonstrated that Toxoplasma actively internalizes exogenous Pi by exploiting a gradient of Na+ ions to drive Pi uptake across the plasma membrane. The Na+-dependent phosphate transport mechanism is electrogenic and functionally coupled to a cipargarmin sensitive Na+-H+-ATPase. Toxoplasma expresses one transmembrane Pi transporter harboring PHO4 binding domains that typify the PiT Family. This transporter named TgPiT, localizes to the plasma membrane, the inward buds of the endosomal organelles termed VAC, and many cytoplasmic vesicles. Upon Pi limitation in the medium, TgPiT is more abundant at the plasma membrane. We genetically ablated the PiT gene, and ΔTgPiT parasites are impaired in importing Pi and synthesizing polyphosphates. Interestingly, ΔTgPiT parasites accumulate 4-times more acidocalcisomes, storage organelles for phosphate molecules, as compared to parental parasites. In addition, these mutants have a reduced cell volume, enlarged VAC organelles, defects in calcium storage and a slightly alkaline pH. Overall, these mutants exhibit severe growth defects and have reduced acute virulence in mice. In survival mode, ΔTgPiT parasites upregulate several genes, including those encoding enzymes that cleave or transfer phosphate groups from phosphometabolites, transporters and ions exchangers localized to VAC or acidocalcisomes. Taken together, these findings point to a critical role of TgPiT for Pi supply for Toxoplasma and also for protection against osmotic stresses.


Assuntos
Osmorregulação/genética , Fosfatos/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato/fisiologia , Toxoplasma , Animais , Animais Geneticamente Modificados , Transporte Biológico/genética , Células Cultivadas , Humanos , Camundongos , Proteínas Cotransportadoras de Sódio-Fosfato/genética , Toxoplasma/genética , Toxoplasma/metabolismo
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