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1.
Parasit Vectors ; 17(1): 252, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858789

RESUMO

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue. METHODS: RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays. RESULTS: The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |log2fold change| â‰§ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes. CONCLUSIONS: Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system.


Assuntos
Testículo , Toxoplasma , Toxoplasmose Animal , Transcriptoma , Animais , Masculino , Camundongos , Testículo/parasitologia , Testículo/metabolismo , Toxoplasma/genética , Toxoplasmose Animal/parasitologia , Espermatogênese/genética , Perfilação da Expressão Gênica , Doença Crônica , Biologia Computacional
2.
Proc Natl Acad Sci U S A ; 121(25): e2314314121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38865262

RESUMO

Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.


Assuntos
Apicoplastos , Ácido Pirúvico , Toxoplasma , Apicoplastos/metabolismo , Toxoplasma/metabolismo , Ácido Pirúvico/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Animais , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Transporte Biológico , Redes e Vias Metabólicas
3.
PLoS One ; 19(6): e0300704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865430

RESUMO

Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.


Assuntos
Eritema Nodoso , Imunoglobulina E , Toxoplasma , Toxoplasmose , Humanos , Toxoplasmose/sangue , Toxoplasmose/complicações , Toxoplasmose/imunologia , Toxoplasmose/epidemiologia , Eritema Nodoso/imunologia , Eritema Nodoso/epidemiologia , Eritema Nodoso/sangue , Feminino , Masculino , Adulto , Imunoglobulina E/sangue , Pessoa de Meia-Idade , Toxoplasma/imunologia , Coinfecção/imunologia , Coinfecção/parasitologia , Mycobacterium leprae/imunologia , Adulto Jovem , Adolescente , Fatores de Risco , Idoso , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/sangue , Hanseníase Virchowiana/epidemiologia
4.
Parasit Vectors ; 17(1): 247, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835064

RESUMO

BACKGROUND: The interplay between Toxoplasma gondii infection and tumor development is intriguing and not yet fully understood. Some studies showed that T. gondii reversed tumor immune suppression, while some reported the opposite, stating that T. gondii infection promoted tumor growth. METHODS: We created three mouse models to investigate the interplay between T. gondii and tumor. Model I aimed to study the effect of tumor growth on T. gondii infection by measuring cyst number and size. Models II and III were used to investigate the effect of different stages of T. gondii infection on tumor development via flow cytometry and bioluminescent imaging. Mouse strains (Kunming, BALB/c, and C57BL/6J) with varying susceptibilities to tumors were used in the study. RESULTS: The size and number of brain cysts in the tumor-infected group were significantly higher, indicating that tumor presence promotes T. gondii growth in the brain. Acute T. gondii infection, before or after tumor cell introduction, decreased tumor growth manifested by reduced bioluminescent signal and tumor size and weight. In the tumor microenvironment, CD4+ and CD8+ T cell number, including their subpopulations (cytotoxic CD8+ T cells and Th1 cells) had a time-dependent increase in the group with acute T. gondii infection compared with the group without infection. However, in the peripheral blood, the increase of T cells, including cytotoxic CD8+ T cells and Th1 cells, persisted 25 days after Lewis lung carcinoma (LLC) cell injection in the group with acute T. gondii. Chronic T. gondii infection enhanced tumor growth as reflected by increase in tumor size and weight. The LLC group with chronic T. gondii infection exhibited decreased percentages of cytotoxic CD8+ T cells and Th1 cells 25 days post-LLC injection as compared with the LLC group without T. gondii infection. At week 4 post-LLC injection, chronic T. gondii infection increased tumor formation rate [odds ratio (OR) 1.71] in both KM and BALB/c mice. CONCLUSIONS: Our research elucidates the dynamics between T. gondii infection and tumorigenesis. Tumor-induced immune suppression promoted T. gondii replication in the brain. Acute and chronic T. gondii infection had opposing effects on tumor development.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Toxoplasma , Animais , Camundongos , Toxoplasma/imunologia , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Feminino , Linfócitos T CD8-Positivos/imunologia , Encéfalo/parasitologia , Encéfalo/patologia , Doença Crônica , Microambiente Tumoral , Neoplasias/parasitologia , Doença Aguda
5.
Sci Rep ; 14(1): 12616, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824180

RESUMO

Toxoplasma infection in humans is considered due to direct contact with infected cats. Toxoplasma infection (an endemic disease) has the potential to affect various organs and systems (brain, eyes, heart, lungs, liver, and lymph nodes). Bilinear incidence rate and constant population (birth rate is equal to death rate) are used in the literature to explain the dynamics of Toxoplasmosis disease transmission in humans and cats. The goal of this study is to consider the mathematical model of Toxoplasma disease with harmonic mean type incident rate and also consider that the population of humans and cats is not equal (birth rate and the death rate are not equal). In examining Toxoplasma transmission dynamics in humans and cats, harmonic mean incidence rates are better than bilinear incidence rates. The disease dynamics are first schematically illustrated, and then the law of mass action is applied to obtain nonlinear ordinary differential equations (ODEs). Analysis of the boundedness, positivity, and equilibrium points of the system has been analyzed. The reproduction number is calculated using the next-generation matrix technique. The stability of disease-free and endemic equilibrium are analyzed. Sensitivity analysis is also done for reproduction number. Numerical simulation shows that the infection is spread in the population when the contact rate ß h and ß c increases while the infection is reduced when the recovery rate δ h increases. This study investigates the impact of various optimal control strategies, such as vaccinations for the control of disease and the awareness of disease awareness, on the management of disease.


Assuntos
Toxoplasmose , Animais , Humanos , Toxoplasmose/transmissão , Toxoplasmose/epidemiologia , Toxoplasmose/prevenção & controle , Gatos , Incidência , Modelos Teóricos , Toxoplasma/patogenicidade , Toxoplasma/fisiologia , Simulação por Computador
6.
Open Biol ; 14(6): 230463, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38835243

RESUMO

Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes, SDH is highly conserved and comprises the following four subunits: SdhA and SdhB form the catalytic core of the complex, while SdhC and SdhD anchor the complex in the membrane. Toxoplasma gondii is an apicomplexan parasite that infects one-third of humans worldwide. The genome of T. gondii encodes homologues of the catalytic subunits SdhA and SdhB, although the physiological role of the SDH complex in the parasite and the identity of the membrane-anchoring subunits are poorly understood. Here, we show that the SDH complex contributes to optimal proliferation and O2 consumption in the disease-causing tachyzoite stage of the T. gondii life cycle. We characterize a small membrane-bound subunit of the SDH complex called mitochondrial protein ookinete developmental defect (MPODD), which is conserved among myzozoans, a phylogenetic grouping that incorporates apicomplexan parasites and their closest free-living relatives. We demonstrate that TgMPODD is essential for SDH activity and plays a key role in attaching the TgSdhA and TgSdhB proteins to the membrane anchor of the complex. Our findings highlight a unique and important feature of mitochondrial energy metabolism in apicomplexan parasites and their relatives.


Assuntos
Proteínas de Protozoários , Succinato Desidrogenase , Toxoplasma , Toxoplasma/metabolismo , Toxoplasma/genética , Toxoplasma/enzimologia , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/química , Humanos , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Mitocôndrias/metabolismo , Filogenia , Animais
7.
Cells ; 13(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38891106

RESUMO

Toxoplasma gondii holds significant therapeutic potential; however, its nonspecific invasiveness results in off-target effects. The purpose of this study is to evaluate whether T. gondii specificity can be improved by surface display of scFv directed against dendritic cells' endocytic receptor, DEC205, and immune checkpoint PD-L1. Anti-DEC205 scFv was anchored to the T. gondii surface either directly via glycosylphosphatidylinositol (GPI) or by fusion with the SAG1 protein. Both constructs were successfully expressed, but the binding results suggested that the anti-DEC-SAG1 scFv had more reliable functionality towards recombinant DEC protein and DEC205-expressing MutuDC cells. Two anti-PD-L1 scFv constructs were developed that differed in the localization of the HA tag. Both constructs were adequately expressed, but the localization of the HA tag determined the functionality by binding to PD-L1 protein. Co-incubation of T. gondii displaying anti-PD-L1 scFv with tumor cells expressing/displaying different levels of PD-L1 showed strong binding depending on the level of available biomarker. Neutralization assays confirmed that binding was due to the specific interaction between anti-PD-L1 scFv and its ligand. A mixed-cell assay showed that T. gondii expressing anti-PD-L1 scFv predominately targets the PD-L1-positive cells, with negligible off-target binding. The recombinant RH-PD-L1-C strain showed increased killing ability on PD-L1+ tumor cell lines compared to the parental strain. Moreover, a co-culture assay of target tumor cells and effector CD8+ T cells showed that our model could inhibit PD1/PD-L1 interaction and potentiate T-cell immune response. These findings highlight surface display of antibody fragments as a promising strategy of targeting replicative T. gondii strains while minimizing nonspecific binding.


Assuntos
Antígeno B7-H1 , Anticorpos de Cadeia Única , Toxoplasma , Toxoplasma/metabolismo , Toxoplasma/imunologia , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo
8.
Proc Natl Acad Sci U S A ; 121(24): e2403054121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38838017

RESUMO

Chronic Toxoplasma gondii infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by T. gondii leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during T. gondii latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.


Assuntos
Encéfalo , Linfócitos T CD8-Positivos , Diferenciação Celular , Toxoplasma , Toxoplasmose , Animais , Linfócitos T CD8-Positivos/imunologia , Toxoplasma/imunologia , Camundongos , Encéfalo/imunologia , Encéfalo/parasitologia , Diferenciação Celular/imunologia , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Infecção Latente/imunologia , Infecção Latente/parasitologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Antígenos CD/genética , Camundongos Endogâmicos C57BL , Feminino
9.
Sci Rep ; 14(1): 13600, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38866852

RESUMO

We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.


Assuntos
Imunoglobulina G , Imunoglobulina M , Inflamação , Saliva , Toxoplasma , Toxoplasmose , Humanos , Masculino , Saliva/metabolismo , Feminino , Adulto , Toxoplasmose/tratamento farmacológico , Toxoplasmose/sangue , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Imunoglobulina G/sangue , Estudos Transversais , Inflamação/metabolismo , Imunoglobulina M/sangue , Imunoglobulina M/metabolismo , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antiprotozoários/imunologia , Simulação por Computador , Estudos Soroepidemiológicos , Adolescente , Simulação de Acoplamento Molecular
10.
J Enzyme Inhib Med Chem ; 39(1): 2346523, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38847581

RESUMO

Toxoplasmosis, induced by the intracellular parasite Toxoplasma gondii, holds considerable implications for global health. While treatment options primarily focusing on folate pathway enzymes have notable limitations, current research endeavours concentrate on pinpointing specific metabolic pathways vital for parasite survival. Carbonic anhydrases (CAs, EC 4.2.1.1) have emerged as potential drug targets due to their role in fundamental reactions critical for various protozoan metabolic processes. Within T. gondii, the Carbonic Anhydrase-Related Protein (TgCA_RP) plays a pivotal role in rhoptry biogenesis. Notably, α-CA (TcCA) from another protozoan, Trypanosoma cruzi, exhibited considerable susceptibility to classical CA inhibitors (CAIs) such as anions, sulphonamides, thiols, and hydroxamates. Here, the recombinant DNA technology was employed to synthesise and clone the identified gene in the T. gondii genome, which encodes an α-CA protein (Tg_CA), with the purpose of heterologously overexpressing its corresponding protein. Tg_CA kinetic constants were determined, and its inhibition patterns explored with inorganic metal-complexing compounds, which are relevant for rational compound design. The significance of this study lies in the potential development of innovative therapeutic strategies that disrupt the vital metabolic pathways crucial for T. gondii survival and virulence. This research may lead to the development of targeted treatments, offering new approaches to manage toxoplasmosis.


Assuntos
Inibidores da Anidrase Carbônica , Anidrases Carbônicas , Clonagem Molecular , Toxoplasma , Toxoplasma/enzimologia , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/genética , Cinética , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/síntese química , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Estrutura Molecular , Ânions/química , Ânions/farmacologia , Ânions/metabolismo
11.
Infect Dis Obstet Gynecol ; 2024: 8844325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883209

RESUMO

Introduction: Transplacental infections are frequent, especially in developing countries, where limited screening is performed to find infectious agents in the pregnant population. We aim to determine the clinical and epidemiological characteristics and seroinfection of antibodies against Toxoplasma, parvovirus B19, T. pallidum, and HIV in pregnant women who attended the Motupe Health Center in Lambayeque, Peru during July-August 2018. Methods: A descriptive cross-sectional study was conducted in 179 pregnant women interviewed with a standardized questionnaire. ELISA was used to determine antibodies to Toxoplasma and parvovirus B19. The detection of syphilis and HIV was conducted using immunochromatography, while the detection of hepatitis B was conducted using FTA-ABS and immunofluorescence, respectively. Results: Of 179 pregnant women, syphilis and HIV infections routinely included in the screening of pregnant women presented a seroinfection of 2.2 and 0.6%, respectively. Toxoplasmosis seroinfection was 25.1%, while IgM antiparvovirus B19 was 40.8%, revealing that pregnant women had an active infection at the time of study. Conclusion: The level of seroinfection of toxoplasmosis reveals the risk to which pregnant women who participated in the study are exposed. The high seroinfection of parvovirus B19 could explain the cases of spontaneous abortion and levels of anemia in newborn that have been reported in Motupe, Lambayeque, Peru. However, future causality studies are necessary to determine the significance of these findings.


Assuntos
Infecções por HIV , Parvovirus B19 Humano , Complicações Infecciosas na Gravidez , Sífilis , Toxoplasma , Toxoplasmose , Treponema pallidum , Humanos , Feminino , Gravidez , Peru/epidemiologia , Treponema pallidum/imunologia , Adulto , Estudos Transversais , Sífilis/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Toxoplasmose/epidemiologia , Toxoplasmose/imunologia , Infecções por HIV/epidemiologia , Toxoplasma/imunologia , Adulto Jovem , Parvovirus B19 Humano/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Adolescente , Estudos Soroepidemiológicos
12.
Vet Parasitol Reg Stud Reports ; 52: 101038, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38880563

RESUMO

Toxoplasmosis is a foodborne disease caused by the protozoan Toxoplasma gondii, and transmitted to humans by eating raw or undercooked meat, mainly. Poultry, beef, and pork are the main meats consumed in Peru; despite this, guinea pig meat is also widely consumed. For this reason, the objective of this study was to molecularly detect T. gondii in domestic and wild guinea pigs from the Marangani district in Cuzco, Peru, and identify some risk factors associated with this pathogen. DNA was extracted from the brain tissue samples of guinea pigs (30 domestic and 30 wild), and PCR protocols were used to amplify the internal transcribed spacer (ITS-1) region and a 529 bp fragment from the T. gondii genome. T. gondii DNA was detected in 14 (23.3%) guinea pigs. T. gondii frequency was 33.3% in domestic guinea pigs and 13.3% in wild guinea pigs. Our results demonstrated that guinea pigs represent an important source for T. gondii infection in human populations in this locality.


Assuntos
Toxoplasma , Toxoplasmose Animal , Animais , Cobaias , Toxoplasma/isolamento & purificação , Toxoplasma/genética , Peru/epidemiologia , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/epidemiologia , DNA de Protozoário/genética , DNA de Protozoário/análise , Animais Selvagens/parasitologia , Feminino , Masculino , Doenças dos Roedores/parasitologia , Doenças dos Roedores/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Animais Domésticos/parasitologia , Fatores de Risco , Prevalência , Encéfalo/parasitologia
13.
Front Immunol ; 15: 1394456, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835777

RESUMO

Introduction: Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Methods: Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Results: Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Discussion: Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.


Assuntos
Biomarcadores , Interleucina-17 , Interleucina-33 , Toxoplasma , Toxoplasmose , Humanos , Feminino , Gravidez , Interleucina-17/sangue , Adulto , Toxoplasmose/sangue , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Toxoplasmose/psicologia , Biomarcadores/sangue , Interleucina-33/sangue , Adulto Jovem , Toxoplasma/imunologia , Adolescente , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/diagnóstico , Depressão/sangue , Depressão/imunologia , Depressão/diagnóstico
14.
Front Cell Infect Microbiol ; 14: 1359888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828265

RESUMO

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Although Toxoplasma secretory proteins during acute infection (tachyzoite, which divides rapidly and causes inflammation) have been extensively characterized, those involved in chronic infection (bradyzoite, which divides slowly and is surrounded by a cyst wall) remain uncertain. Regulation of the cyst wall is essential to the parasite life cycle, and polysaccharides, such as chitin, in the cyst wall are necessary to sustain latent infection. Toxoplasma secretory proteins during the bradyzoite stage may have important roles in regulating the cyst wall via polysaccharides. Here, we focused on characterizing the hypothetical T. gondii chitinase, chitinase-like protein 1 (TgCLP1). We found that the chitinase-like domain containing TgCLP1 is partially present in the bradyzoite microneme and confirmed, albeit partially, its previous identification in the tachyzoite microneme. Furthermore, although parasites lacking TgCLP1 could convert from tachyzoites to bradyzoites and make an intact cyst wall, they failed to convert from bradyzoites to tachyzoites, indicating that TgCLP1 is necessary for bradyzoite reactivation. Taken together, our findings deepen our understanding of the molecular basis of recrudescence and could contribute to the development of novel strategies for the control of toxoplasmosis.


Assuntos
Quitinases , Proteínas de Protozoários , Toxoplasma , Toxoplasmose , Toxoplasma/genética , Toxoplasma/metabolismo , Toxoplasma/enzimologia , Animais , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Quitinases/metabolismo , Quitinases/genética , Toxoplasmose/parasitologia , Humanos , Camundongos , Estágios do Ciclo de Vida
15.
Sci Total Environ ; 935: 173290, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38782291

RESUMO

Toxoplasmosis is a parasitic zoonosis of key importance in veterinary and public health. This article summarizes the available data (from 2000 to 2023) of exposition to Toxoplasma gondii in wildlife species in Spain based on a systematic bibliographic search, as well as further analysis of its potential relationship with environmental variables, biodiversity, anthropogenic impact on the habitat, and the reported human cases of toxoplasmosis. The overall seroprevalence of T. gondii in carnivorous mammals, birds, ungulate and lagomorph species in Spain was estimated at 69.3 %, 36.4 %, 18.4 %, and 16.2 %, respectively. Among the studies considered, great heterogeneity was observed both between and within taxonomic groups [Cohen's d > 0.8; X2 = 1039.10, df = 4 (p < 0.01) I2 = 97 %, r2 = 1.88, (p < 0.001)] and between and within bioregions [Cohen's d > 0.5; X2 = 368.59, df = 4 (p < 0.01)]. The results of a generalized linear model explaining T. gondii seroprevalence in wild animals suggest the influence of abiotic variables [wetland (p < 0.001), unvegetated (p < 0.001), isothermality (p < 0.001), and mean temperature during wettest quarter (p < 0.05)] and number of intermediate host species as positively associated with increased exposure of wildlife to T. gondii (p < 0.01). Toxoplasma gondii DNA was detected in both wild birds and wild mammals (range: 0.0-51.2 %) mainly from north-centre, northeast, and central-west of Spain. Regarding hospitalisation rates due to toxoplasmosis in humans, some abiotic variables [permanent crops (p < 0.05) and mean temperature during wettest quarter (p < 0.05)] showed a positive association. Despite certain limitations, this research evidences a substantial gap of knowledge on the implication of wildlife in the life cycle of T. gondii in Spain. This lack of knowledge is particularly evident in areas where the human-livestock-wildlife interface overlaps, preventing us from accurately determining its true distribution in different habitats, as well as its potential direct or indirect implications on public and veterinary health.


Assuntos
Animais Selvagens , Toxoplasma , Toxoplasmose Animal , Animais , Espanha/epidemiologia , Humanos , Toxoplasmose Animal/epidemiologia , Animais Domésticos , Estudos Soroepidemiológicos , Zoonoses/epidemiologia , Toxoplasmose/epidemiologia
16.
J Clin Microbiol ; 62(6): e0169723, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38780287

RESUMO

For decades, an immunosorbent agglutination assay (ISAGA) has been considered the gold standard method for the detection of Toxoplasma gondii-specific IgM in infants for the diagnosis of congenital toxoplasmosis (CT). The Toxoplasma IgM ISAGA was consistently reported as having superior sensitivity. Unfortunately, the commercial kit for the detection of Toxoplasma IgM ISAGA will no longer be available in 2024 and alternatives will only be available at a handful of reference laboratories as in-house or laboratory-developed tests. In a recent study, S. Arkhis, C. Rouges, N. Dahane, H. Guegan, et al. (J Clin Microbiol 62:e01222-23, 2024, https://doi.org/10.1128/jcm.01222-23), reported that the performance of the PLATELIA Toxo IgM was comparable to that of the ISAGA method for the diagnosis of CT. A second study revealing similar results supports the PLATELIA Toxo IgM as the new gold standard for the detection of T. gondii-specific IgM in infants. Although the laboratory toolbox for CT diagnosis has been reshuffled successfully, it is by universally implementing all available serological and molecular tools at the earliest possible time during gestation that we can best defend children's brain from the potential harm caused by trans-placentally transmitted T. gondii.


Assuntos
Anticorpos Antiprotozoários , Imunoglobulina M , Toxoplasma , Toxoplasmose Congênita , Humanos , Toxoplasmose Congênita/diagnóstico , Imunoglobulina M/sangue , Toxoplasma/imunologia , Toxoplasma/isolamento & purificação , Anticorpos Antiprotozoários/sangue , Lactente , Sensibilidade e Especificidade , Recém-Nascido , Testes de Aglutinação/métodos
17.
Parasitol Res ; 123(5): 217, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772951

RESUMO

Toxoplasmosis poses a global health threat, ranging from asymptomatic cases to severe, potentially fatal manifestations, especially in immunocompromised individuals and congenital transmission. Prior research suggests that oregano essential oil (OEO) exhibits diverse biological effects, including antiparasitic activity against Toxoplasma gondii. Given concerns about current treatments, exploring new compounds is important. This study was to assess the toxicity of OEO on BeWo cells and T. gondii tachyzoites, as well as to evaluate its effectiveness in in vitro infection models and determine its direct action on free tachyzoites. OEO toxicity on BeWo cells and T. gondii tachyzoites was assessed by MTT and trypan blue methods, determining cytotoxic concentration (CC50), inhibitory concentration (IC50), and selectivity index (SI). Infection and proliferation indices were analyzed. Direct assessments of the parasite included reactive oxygen species (ROS) levels, mitochondrial membrane potential, necrosis, and apoptosis, as well as electron microscopy. Oregano oil exhibited low cytotoxicity on BeWo cells (CC50: 114.8 µg/mL ± 0.01) and reduced parasite viability (IC50 12.5 ± 0.06 µg/mL), demonstrating 9.18 times greater selectivity for parasites than BeWo cells. OEO treatment significantly decreased intracellular proliferation in infected cells by 84% after 24 h with 50 µg/mL. Mechanistic investigations revealed increased ROS levels, mitochondrial depolarization, and lipid droplet formation, linked to autophagy induction and plasma membrane permeabilization. These alterations, observed through electron microscopy, suggested a necrotic process confirmed by propidium iodide labeling. OEO treatment demonstrated anti-T. gondii action through cellular and metabolic change while maintaining low toxicity to trophoblastic cells.


Assuntos
Autofagia , Óleos Voláteis , Origanum , Espécies Reativas de Oxigênio , Toxoplasma , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Origanum/química , Humanos , Autofagia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Antiprotozoários/farmacologia , Concentração Inibidora 50 , Necrose/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
18.
Immunity ; 57(5): 1005-1018.e7, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697116

RESUMO

Cytokine expression during T cell differentiation is a highly regulated process that involves long-range promoter-enhancer and CTCF-CTCF contacts at cytokine loci. Here, we investigated the impact of dynamic chromatin loop formation within the topologically associating domain (TAD) in regulating the expression of interferon gamma (IFN-γ) and interleukin-22 (IL-22); these cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. In situ Hi-C analyses revealed inducible TADs that insulated Ifng and Il22 enhancers during Th1 cell differentiation. Targeted deletion of a 17 bp boundary motif of these TADs imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo, upon Toxoplasma gondii infection. In contrast, this boundary element was dispensable for cytokine regulation in natural killer cells. Our findings suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.


Assuntos
Fator de Ligação a CCCTC , Diferenciação Celular , Interferon gama , Interleucina 22 , Interleucinas , Células Th1 , Animais , Fator de Ligação a CCCTC/metabolismo , Fator de Ligação a CCCTC/genética , Células Th1/imunologia , Camundongos , Diferenciação Celular/imunologia , Interferon gama/metabolismo , Sítios de Ligação , Interleucinas/metabolismo , Interleucinas/genética , Elementos Facilitadores Genéticos/genética , Camundongos Endogâmicos C57BL , Cromatina/metabolismo , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Toxoplasmose/genética , Regulação da Expressão Gênica , Toxoplasma/imunologia , Citocinas/metabolismo , Linhagem da Célula , Células Th17/imunologia
19.
Indian J Ophthalmol ; 72(6): 772-774, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38804796

RESUMO

A 33-year-old male presented with unilateral painless vision loss with a history of sub-tenon steroid for the same. The fundus showed an elevated focus of retinochoroiditis with vitritis. On investigating for the cause, polymerase chain reaction test on the anterior chamber tap was found to be positive for Toxoplasma. Such confusing and atypical cases usually produce a clinical dilemma and should be managed in a stepwise manner. Ancillary investigations usually provide a clue to the clinician and should be performed without any hesitation.


Assuntos
Toxoplasma , Toxoplasmose Ocular , Humanos , Masculino , Adulto , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasma/isolamento & purificação , Toxoplasma/genética , Reação em Cadeia da Polimerase , Coriorretinite/diagnóstico , Coriorretinite/parasitologia , Fundo de Olho , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , DNA de Protozoário/análise , Diagnóstico Diferencial , Angiofluoresceinografia/métodos
20.
PLoS Negl Trop Dis ; 18(5): e0011335, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38805559

RESUMO

BACKGROUND: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. OBJECTIVES: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. METHODS: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. FINDINGS: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. CONCLUSIONS/SIGNIFICANCE: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. TRIAL REGISTRATION: NCT04474132, https://clinicaltrials.gov/study/NCT04474132 ClinicalTrials.gov.


Assuntos
Toxoplasmose Congênita , Feminino , Humanos , Recém-Nascido , Gravidez , Anticorpos Antiprotozoários/sangue , Reações Falso-Positivas , Imunoglobulina M/sangue , Diagnóstico Pré-Natal/métodos , Sensibilidade e Especificidade , Toxoplasma/imunologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/prevenção & controle
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