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2.
Exp Parasitol ; 218: 108006, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32991867

RESUMO

This study aimed to elucidate the cellular immune response against Toxoplasma gondii in chronically infected mice reinfected with different strains of the parasite to elucidate the immunological basis for chronicity or virulence and to uncover the involvement of genes that encode virulence proteins and modulate the immune response. BALB/c mice were infected by oral gavage with non-virulent D8 strain and challenged 45 days post-infection with virulent EGS or CH3 strains. Cytokine measurement was performed 2 days post-challenge in cell extracts of the small intestine and 2, 7, and 14 days post-challenge in serum. Virulence gene allele type of these strains was analyzed. Challenged mice survived by avoiding exacerbated inflammation and inhibiting the overproduction of cytokines. Local and systemic cytokine response in challenged mice was similar to chronic controls and quite distinct in mice acutely infected with the EGS or CH3 strains. Allelic combinations of the virulence genes ROP5/ROP18 was predictive of virulence in mice when tested in these T. gondii strains. Other allelic combinations of rhoptries and dense granules genes showed discrepancies.


Assuntos
Citocinas/biossíntese , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Alelos , Animais , Doença Crônica , Citocinas/sangue , Citocinas/genética , Cães , Feminino , Íleo/imunologia , Imunidade Celular , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Proteínas de Protozoários/genética , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Virulência
3.
BMC Infect Dis ; 20(1): 694, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962648

RESUMO

BACKGROUND: Toxoplasma gondii infection endangers human health and affects animal husbandry. Serological detection is the main method used for epidemiological investigations and diagnosis of toxoplasmosis. The key to effective diagnosis of toxoplasmosis is the use of a standardized antigen and a specific and sensitive detection method. Peroxiredoxin is an antigenic protein and vaccine candidate antigen of T. gondii that has not yet been exploited for diagnostic application. METHODS: In this study, recombinant T. gondii peroxiredoxin protein (rTgPrx) was prepared and used in dot-immunogold-silver staining (Dot-IGSS) to detect IgG antibodies in serum from mice and pregnant women. The rTgPrx-Dot-IGSS method was established and optimized using mouse serum. Furthermore, serum samples from pregnant women were analyzed by rTgPrx-Dot-IGSS. RESULTS: Forty serum samples from mice infected with T. gondii and twenty negative serum samples were analyzed. The sensitivity and specificity of rTgPrx-Dot-IGSS were 97.5 and 100%, respectively, equivalent to those of a commercial ELISA kit for anti-Toxoplasma IgG antibody. Furthermore, 540 serum samples from pregnant women were screened with a commercial ELISA kit. Eighty-three positive and 60 negative serum samples were analyzed by rTgPrx-Dot-IGSS. The positive rate was 95.18%, comparable to that obtained with the commercial ELISA kit. CONCLUSIONS: The Dot-IGSS method with rTgPrx as an antigen might be useful for diagnosing T. gondii infection in individuals.


Assuntos
Imuno-Histoquímica/métodos , Peroxirredoxinas/imunologia , Complicações Parasitárias na Gravidez , Toxoplasmose/diagnóstico , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Camundongos , Peroxirredoxinas/genética , Gravidez , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Coloração pela Prata , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/parasitologia
4.
Parasitol Res ; 119(10): 3165-3180, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32789534

RESUMO

Parasitic diseases affect more than one billion people worldwide, and most of them are chronic conditions in which the treatment and prevention are difficult. The appearance of granulomas, defined as organized and compact structures of macrophages and other immune cells, during various parasitic diseases is frequent, since these structures will only form when individual immune cells do not control the invading agent. Th2-typering various parasitic diseases are frequent, since these structures will only form when individual immune cells do not control the invading agent. The characterization of granulomas in different parasitic diseases, as well as recent findings in this field, is discussed in this review, in order to understand the significance of the granuloma and its modulation in the host-parasite interaction and in the immune, pathological, and parasitological aspects of this interaction. The parasitic granulomatous diseases granulomatous amebic encephalitis, toxoplasmosis, leishmaniasis, neurocysticercosis, and schistosomiasis mansoni are discussed as well as the mechanistic and dynamical aspects of the infectious granulomas.


Assuntos
Granuloma/imunologia , Granuloma/patologia , Macrófagos/imunologia , Neurocisticercose/imunologia , Esquistossomose mansoni/imunologia , Toxoplasmose/imunologia , Animais , Granuloma/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Macrófagos/patologia , Neurocisticercose/patologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/patologia , Taenia solium/imunologia , Toxoplasma/imunologia , Toxoplasmose/patologia
5.
PLoS Pathog ; 16(8): e1008327, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853276

RESUMO

Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are not fully elucidated, we investigated requirements for eliciting naïve CD8 T cell IFNγ responses to a vacuolar resident antigen of T. gondii, TGD057. Naïve TGD057 antigen-specific CD8 T cells (T57) were isolated from transnuclear mice and responded to parasite-infected bone marrow-derived macrophages (BMDMs) in an antigen-dependent manner, first by producing IL-2 and then IFNγ. T57 IFNγ responses to TGD057 were independent of the parasite's protein export machinery ASP5 and MYR1. Instead, host immunity pathways downstream of the regulatory Immunity-Related GTPases (IRG), including partial dependence on Guanylate-Binding Proteins, are required. Multiple T. gondii ROP5 isoforms and allele types, including 'avirulent' ROP5A from clade A and D parasite strains, were able to suppress CD8 T cell IFNγ responses to parasite-infected BMDMs. Phenotypic variance between clades B, C, D, F, and A strains suggest T57 IFNγ differentiation occurs independently of parasite virulence or any known IRG-ROP5 interaction. Consistent with this, removal of ROP5 is not enough to elicit maximal CD8 T cell IFNγ production to parasite-infected cells. Instead, macrophage expression of the pathogen sensors, NLRP3 and to a large extent NLRP1, were absolute requirements. Other members of the conventional inflammasome cascade are only partially required, as revealed by decreased but not abrogated T57 IFNγ responses to parasite-infected ASC, caspase-1/11, and gasdermin D deficient cells. Moreover, IFNγ production was only partially reduced in the absence of IL-12, IL-18 or IL-1R signaling. In summary, T. gondii effectors and host machinery that modulate parasitophorous vacuolar membranes, as well as NLR-dependent but inflammasome-independent pathways, determine the full commitment of CD8 T cells IFNγ responses to a vacuolar antigen.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Inflamassomos/imunologia , Interferon gama/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Protozoários/metabolismo , Transdução de Sinais , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Animais , Linfócitos T CD8-Positivos/parasitologia , Feminino , Macrófagos/imunologia , Macrófagos/parasitologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas de Protozoários/genética , Toxoplasmose Animal/parasitologia , Vacúolos/imunologia , Vacúolos/metabolismo , Vacúolos/parasitologia , Virulência/imunologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-32635389

RESUMO

Toxoplasmosis is a disease caused by the protozoan parasite Toxoplasma gondii (T. gondii). Human toxoplasmosis seroprevalence in Malaysia has increased since it was first reported in 1973 as shown in previous reviews of 1991 and 2007. However, over a decade since the last review, comprehensive data on toxoplasmosis in Malaysia is lacking. This work aimed at reviewing articles on toxoplasmosis research in Malaysia in order to identify the research gaps, create public awareness, and efforts made so far and proffer management options on the disease. The present review examines the available published research articles from 2008 to 2018 related to toxoplasmosis research conducted in Malaysia. The articles reviewed were retrieved from nine credible databases such as Web of Science, Google Scholar, ScienceDirect, PubMed, Scopus, Springer, Wiley online library, Ovid, and Cochrane using the keywords; Malaysia, toxoplasmosis, Toxoplasma gondii, toxoplasma encephalitis, seroprevalence, human immunodeficiency virus (HIV) patients, pregnant women, genotype strain, anti-toxoplasma antibodies, felines, and vaccine. The data highlighted seropositive cases from healthy community members in Pangkor Island (59.7%) and among migrant workers (57.4%) at alarming rates, as well as 42.5% in pregnant women. Data on animal seroprevalence were limited and there was no information on cats as the definitive host. Genetic characterization of Toxoplasma gondii from HIV patients; pregnant women, and domestic cats is lacking. This present review on toxoplasmosis is beneficial to researchers, health workers, animal health professionals, and policymakers. Therefore, attention is required to educate and enlighten health workers and the general public about the risk factors associated with T. gondii infection in Malaysia.


Assuntos
Toxoplasmose Animal/epidemiologia , Toxoplasmose/epidemiologia , Idoso de 80 Anos ou mais , Animais , Anticorpos Antiprotozoários , Gatos , Estudos Transversais , Infecções por HIV , Humanos , Malásia/epidemiologia , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasma/imunologia
7.
PLoS One ; 15(7): e0235463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609758

RESUMO

INTRODUCTION: Sleepiness is the main clinical expression of obstructive sleep apnea (OSA) syndrome resulting from upper airway collapse. Recent studies have discussed the fact that the presence of T. gondii cysts in the brain and the resulting biochemical and immunological mechanisms could be linked to neurobehavioral disorders. The aim of the present study was to explore the potential impact of chronic toxoplasmosis on sleepiness and on obstructive sleep apnea (OSA) severity in OSA obese patients. MATERIALS AND METHODS: A case control study on obese patients screened for OSA was performed. According to the sleep disorder and matched based on gender, age and body mass index (BMI), two groups of obese patients were selected from our sample collection database. All patients were tested for toxoplasmosis serological status measuring anti-Toxoplasma IgG and IgM levels. Univariable and multivariable logistic regression models were performed to assess the impact of chronic toxoplasmosis on sleepiness and OSA severity. RESULTS: 107 obese patients suffering from OSA were included in the study (median age: 53.3 years Interquartile range (IQR): [41.9-59.9]; median BMI: 39.4 kg/m2 IQR: [35.5-44.1], apnea-hypopnea index = 27.5 events/h [10.7-49.9]). Chronic toxoplasmosis was present in 63.4% and 70.7% of patients with or without sleepiness (p = 0.48), respectively and was not associated either to sleepiness (OR: 0.76, 95% CI: [0.52; 2.33], p = 0.64) or OSA severity (OR = 1.75, 95% CI: [0.51; 5.98] p = 0.37). CONCLUSION: Although chronic Toxoplasma infection in immunocompetent humans has been associated to several behavioral disorders or pathologies in recent literature, we demonstrate here that chronic toxoplasmosis is not associated to sleepiness and to sleep apnea syndrome severity in obese patients suspected of sleep apnea syndrome.


Assuntos
Doença Crônica/epidemiologia , Obesidade/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Toxoplasmose Cerebral/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Sonolência , Toxoplasma/imunologia , Toxoplasmose Cerebral/imunologia
8.
Nat Commun ; 11(1): 3687, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703941

RESUMO

Microglia, resident immune cells of the CNS, are thought to defend against infections. Toxoplasma gondii is an opportunistic infection that can cause severe neurological disease. Here we report that during T. gondii infection a strong NF-κB and inflammatory cytokine transcriptional signature is overrepresented in blood-derived macrophages versus microglia. Interestingly, IL-1α is enriched in microglia and IL-1ß in macrophages. We find that mice lacking IL-1R1 or IL-1α, but not IL-1ß, have impaired parasite control and immune cell infiltration within the brain. Further, we show that microglia, not peripheral myeloid cells, release IL-1α ex vivo. Finally, we show that ex vivo IL-1α release is gasdermin-D dependent, and that gasdermin-D and caspase-1/11 deficient mice show deficits in brain inflammation and parasite control. These results demonstrate that microglia and macrophages are differently equipped to propagate inflammation, and that in chronic T. gondii infection, microglia can release the alarmin IL-1α, promoting neuroinflammation and parasite control.


Assuntos
Interleucina-1alfa/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Microglia/imunologia , Proteínas de Ligação a Fosfato/metabolismo , Toxoplasma/imunologia , Toxoplasmose Cerebral/imunologia , Animais , Encéfalo/citologia , Encéfalo/imunologia , Encéfalo/parasitologia , Encéfalo/patologia , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Humanos , Interleucina-1alfa/genética , Interleucina-1alfa/imunologia , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Microglia/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/sangue , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Cerebral/patologia
9.
Arch Microbiol ; 202(10): 2689-2695, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32725599

RESUMO

Depression disorder is one of the most common psychological recognitions that characterized by sadness, low self-confidence, and disinterest in every activity. Considering evidence showing the effects of toxoplasmosis on the psychological disease, this study conducted to investigate the serological and molecular aspects of Toxoplasma gondii infection among patients with depression. In this study, after selecting the patients with depression and control groups under the supervision of a psychologist, the blood samples were collected and the serum samples and buffy coat were separated. The specific anti-Toxoplasma IgG antibodies in serum samples were evaluated using the commercial ELISA kit. Then the desired region of the Toxoplasma B1 gene was amplified using the specific primers. To confirm the specificity of primers to amplify the B1 gene of Toxoplasma, the extracted PCR product was sequenced. The overall prevalence of toxoplasmosis in patients with depression was 59.8 and 60.19% by ELISA and PCR, respectively. In the control group, the prevalence of Toxoplasma was 56.3 and 40.2% by serology and PCR. There was a significant correlation between the prevalence of toxoplasmosis and depression. Moreover, a significant difference was found between the variables of age, sex, kind of nutrition, level of education and toxoplasmosis among the two cases and control groups. The higher prevalence of Toxoplasma infection among patients with depression compared with the control group indicates the probable impact of this parasite on depression and exacerbates its symptoms, which requires special attention of specialist physicians and patient's relatives.


Assuntos
Anticorpos Antiprotozoários/sangue , Depressão/complicações , Depressão/parasitologia , Toxoplasma , Toxoplasmose/complicações , Toxoplasmose/epidemiologia , Anticorpos Antiprotozoários/genética , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Genes de Protozoários/genética , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/imunologia
10.
Parasitol Res ; 119(9): 2897-2905, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32677001

RESUMO

The central nervous system of the intermediate host plays a central role in lifelong persistence of Toxoplasma gondii as well as the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised individuals. The purinergic system has been implicated in a wide range of immunological pathways for controlling intracellular responses to pathogens, including T. gondii. In the present study, we investigated the effect of resveratrol (RSV) on ectonucleotidases, adenosine deaminase (ADA), and purinergic receptors during chronic infection by T. gondii. For this study, Swiss mice were divided into control (CTL), resveratrol (RSV), infected (INF), and INF+RSV groups. The animals were orally infected with the VEG strain and treated with RSV (100 mg/kg, orally). Ectonucleotidase activities, P2X7, P2Y1, A1, and A2A purinergic receptor density, ROS, and thiobarbituric acid reactive substances levels were measured in the cerebral cortex of mice. T. gondii infection increased NTPDase and reduced ADA activities. Treatment with RSV also affected enzymes hydrolysing extracellular nucleotides and nucleosides. Finally, RSV affected P1 and P2 purinergic receptor expression during T. gondii infection. Overall, RSV-mediated beneficial changes in purinergic signalling and oxidative stress, possibly improving cerebral cortex homeostasis in T. gondii infection.


Assuntos
Córtex Cerebral/parasitologia , Inibidores Enzimáticos/farmacologia , Fármacos Neuroprotetores/farmacologia , Resveratrol/farmacologia , Toxoplasmose Animal/tratamento farmacológico , Adenosina Desaminase/metabolismo , Animais , Camundongos , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Toxoplasma/imunologia
11.
Parasitol Res ; 119(9): 2907-2916, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32686022

RESUMO

The protozoan parasite Toxoplasma gondii secretes a number of dense granule proteins (GRAs) from the dense granule organelle to manipulate the host cell. Two of these effector proteins (GRA17 and GRA23) are involved in the trafficking of molecules between the parasitophorous vacuole (PV) and the host cell cytoplasm. However, their roles in establishing chronic infection remain obscured. In this study, CRISPR-Cas9 was used to delete gra17 or gra23 gene in T. gondii Pru strain (type II). The growth, the virulence, the ability to establish chronic infection, and the immunogenicity of the constructed mutant strains were investigated in Kunming mice. Pru:Δgra17 and Pru:Δgra23 mutants developed PVs with abnormal morphology and exhibited reduced growth rate, compared with the wild-type Pru strain. Deletion of gra17 abrogated acute infection and blocked cyst formation. Although the deletion of gra23 caused slight attenuation of the parasite virulence in mice, it caused a significant reduction in cyst formation. Immunization with Pru:Δgra17 induced high levels of IgG (IgG1 and IgG2a) antibodies and cytokines (interleukin-2 [IL-2], IL-10, IL-12, and interferon gamma [IFN-γ]), which conferred significant protection in mice challenged with virulent type I (RH), ToxoDB#9 (PYS) strains, or less virulent type II (Pru) strain of T. gondii. These findings show that GRA17 and GRA23 play important roles in T. gondii chronic infection and that irreversible deletion of gra17 in T. gondii type II Pru strain can be a viable option for stimulating protective immunity to T. gondii infection.


Assuntos
Antígenos de Protozoários/imunologia , Citocinas/metabolismo , Proteínas de Protozoários/genética , Toxoplasma , Fatores de Virulência/genética , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Toxoplasma/genética , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Virulência/genética
12.
Adv Clin Exp Med ; 29(6): 669-675, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32573993

RESUMO

BACKGROUND: Toxoplasma gondii (T. gondii) is a ubiquitous protozoan parasite which causes a serious disease called toxoplasmosis. The high prevalence of T. gondii infection has attracted a great deal of interest in its diagnosis and treatment. The use of pure antigens shows high sensitivity and specificity, but challenges such as cross-reactivity remain diagnostic difficulties. OBJECTIVES: The aim of this study was to use 3 surface antigens (SAGs) of T. gondii to design gene-encoding a multi-epitope and immunogenic protein as a serodiagnostic marker. MATERIAL AND METHODS: The multi-epitope antigen was expressed using Escherichia coli BL21 (DE3) cells and purified using affinity chromatography. To evaluate acute toxoplasmosis, 95 human sera with anti-T. gondii IgG, 25 human sera without anti-T. gondii IgG and 6 serum samples with nosocomial infections were collected and submitted to an enzyme-linked immunosorbent assay (ELISA) analysis. The potential of purified protein as a diagnostic marker of T. gondii infection was also investigated using ELISA analysis. RESULTS: The western blot analysis for both protein expression and purification confirmed that the protein was expressed and purified successfully. The results of validation showed a sensitivity of 72.6% and a specificity of 90.3% for recombinant ELISA. CONCLUSIONS: Although this protein showed potential for detecting T. gondii, the sensitivity and specificity were lower than in tests that use the whole body of the parasite.


Assuntos
Antígenos de Protozoários , Toxoplasma , Toxoplasmose , Antígenos de Protozoários/análise , Ensaio de Imunoadsorção Enzimática , Epitopos , Humanos , Proteínas Recombinantes , Sensibilidade e Especificidade , Testes Sorológicos , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Toxoplasmose/genética
13.
BMC Infect Dis ; 20(1): 415, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539811

RESUMO

BACKGROUND: Mounting evidence suggested a complex correlation between host lipid metabolism and Toxoplasma gondii (T. gondii) infection. However, the inherent association between T. gondii infection and host lipid state remains elusive either in mice or in human hosts. METHODS: Through a study in a sample of 1045 healthy participants from eastern China, we determined the association of T. gondii infection and host lipid levels using serological methods. We then examined the host lipid levels in C57BL/6 J mice at both acute and chronic T. gondii infection stages (for a period up to 36 weeks post infection). RESULTS: In our case-control study, T. gondii seropositive individuals had higher low-density lipoproteins (LDL) (P = 0.0043) and total cholesterol (TC) (P = 0.0134) levels compared to seronegative individuals. Furthermore, individuals with LDL (OR = 3.25; 95% CI:1.60-6.61) and TC (OR = 2.10; 95% CI:1.22-3.63) levels above the upper limit of normal range had higher odds ratio to be T. gondii IgG positive. Consistently, in vivo data revealed that a significantly increased LDL level was first observed at early acute stage but plateaued to later time (chronic infection with T. gondii). CONCLUSIONS: In both healthy population and T. gondii-infected mice, seropositive individuals had higher LDL level. Individuals with positive T. gondii IgG had more odds of being with LDL and TC abnormality. Latent T. gondii infection is common worldwide, potential medical interventions to host lipid metabolism may be a breakthrough point to the prevention and control of this parasite infection.


Assuntos
Metabolismo dos Lipídeos , Toxoplasma/fisiologia , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Estudos de Casos e Controles , China/epidemiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Razão de Chances , Toxoplasma/imunologia , Toxoplasmose/sangue
14.
J Parasitol ; 106(3): 392-394, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32556162

RESUMO

The objective of the study was to identify the seroprevalence of anti-Toxoplasma gondii antibodies in sheep herds from 3 municipalities from Jalisco, Mexico, as well as estimate the association between seroprevalence and certain factors presents in the farms. In total, 12 sheep farms that maintain only hair breeds were included in the work. From these farms, 336 blood samples were collected, corresponding 324 to ewes and 12 rams. Serum samples were subjected to ELISA test, and the association between the frequency of antibodies and some potential risk factors was estimated. The overall seroprevalence to anti-T. gondii antibodies in the population studied was 17.8% (60/336; 95% confidence interval [C.I.] 14-22), all farms had positive animals, and the seroprevalence of antibodies ranged between 7 to 32%. Seroprevalence in specific municipalities was 18.7% in Lagos de Moreno, 17.8% in Encarnación de Díaz, and 16.9% in San Juan de los Lagos. Seroprevalence in ewes was 17.5% (57/324; 95% C.I. 13-22), and seroprevalence in rams was 25% (3/12; 95% C.I. 6-57), while among breeds it was 17.8% in Pelibuey (20/112; 95% C.I. 11-26), 16.6% in Kathadin (14/84; 95% C.I. 9-26), 15.4% in Blackbelly (13/84; 95% C.I. 8-25), and 23.2% in Dorper (13/56; 95% C.I. 13-36); no differences were observed among breeds (p < 0.05). The presence of cats on the farms was associated with seroprevalence (odds ratio [OR] 2.8; 95% C.I. 1.8-7.3, p < 0.001), as was the absence of a rodent-control program (OR 1.5; 95% C.I. 0.8-3.2, p < 0.05). No other factors were identified as associated with seroprevalence.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças dos Ovinos/parasitologia , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Animais , Gatos , Feminino , Masculino , México/epidemiologia , Controle de Pragas/estatística & dados numéricos , Ratos , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/transmissão , Inquéritos e Questionários , Toxoplasmose Animal/imunologia , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/transmissão
15.
PLoS Pathog ; 16(5): e1008586, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453782

RESUMO

The murine innate immune response against Toxoplasma gondii is predominated by the interaction of TLR11/12 with Toxoplasma profilin. However, mice lacking Tlr11 or humans, who do not have functional TLR11 or TLR12, still elicit a strong innate immune response upon Toxoplasma infection. The parasite factors that determine this immune response are largely unknown. Herein, we investigated two dense granule proteins (GRAs) secreted by Toxoplasma, GRA15 and GRA24, for their role in stimulating the innate immune response in Tlr11-/- mice and in human cells, which naturally lack TLR11/TLR12. Our results show that GRA15 and GRA24 synergistically shape the early immune response and parasite virulence in Tlr11-/- mice, with GRA15 as the predominant effector. Nevertheless, acute virulence in Tlr11-/- mice is still dominated by allelic combinations of ROP18 and ROP5, which are effectors that determine evasion of the immunity-related GTPases. In human macrophages, GRA15 and GRA24 play a major role in the induction of IL12, IL18 and IL1ß secretion. We further show that GRA15/GRA24-mediated IL12, IL18 and IL1ß secretion activates IFNγ secretion by peripheral blood mononuclear cells (PBMCs), which controls Toxoplasma proliferation. Taken together, our study demonstrates the important role of GRA15 and GRA24 in activating the innate immune response in hosts lacking TLR11.


Assuntos
Imunidade Inata/imunologia , Macrófagos/imunologia , Proteínas de Protozoários/imunologia , Receptores Toll-Like/imunologia , Toxoplasma/imunologia , Toxoplasmose/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Humanos , Imunidade Inata/genética , Macrófagos/parasitologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Células RAW 264.7 , Receptores Toll-Like/genética , Toxoplasmose/genética , Toxoplasmose/patologia
16.
PLoS Pathog ; 16(5): e1008572, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32413093

RESUMO

The apicomplexan Toxoplasma gondii induces strong protective immunity dependent upon recognition by Toll-like receptors (TLR)11 and 12 operating in conjunction with MyD88 in the murine host. However, TLR11 and 12 proteins are not present in humans, inspiring us to investigate MyD88-independent pathways of resistance. Using bicistronic IL-12-YFP reporter mice on MyD88+/+ and MyD88-/- genetic backgrounds, we show that CD11c+MHCII+F4/80- dendritic cells, F4/80+ macrophages, and Ly6G+ neutrophils were the dominant cellular sources of IL-12 in both wild type and MyD88 deficient mice after parasite challenge. Parasite dense granule protein GRA24 induces p38 MAPK activation and subsequent IL-12 production in host macrophages. We show that Toxoplasma triggers an early and late p38 MAPK phosphorylation response in MyD88+/+ and MyD88-/- bone marrow-derived macrophages. Using the uracil auxotrophic Type I T. gondii strain cps1-1, we demonstrate that the late response does not require active parasite proliferation, but strictly depends upon GRA24. By i. p. inoculation with cps1-1 and cps1-1:Δgra24, we identified unique subsets of chemokines and cytokines that were up and downregulated by GRA24. Finally, we demonstrate that cps1-1 triggers a strong host-protective GRA24-dependent Th1 response in the absence of MyD88. Our data identify GRA24 as a major mediator of p38 MAPK activation, IL-12 induction and protective immunity that operates independently of the TLR/MyD88 cascade.


Assuntos
Interleucina-12/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Proteínas de Protozoários/imunologia , Toxoplasma/imunologia , Toxoplasmose/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Animais , Ativação Enzimática/genética , Ativação Enzimática/imunologia , Interleucina-12/genética , Sistema de Sinalização das MAP Quinases/genética , Macrófagos/parasitologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Proteínas de Protozoários/genética , Toxoplasma/genética , Toxoplasmose/genética , Toxoplasmose/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
17.
PLoS One ; 15(5): e0233305, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413075

RESUMO

Despite vulnerability and unsanitary conditions of animal hoarding may predispose environmental contamination and spread of vectors and pathogens, no study to date has focused on their impact on public health and zoonotic diseases. Accordingly, this study aimed to assess the seroprevalence of anti-Toxoplasma gondii antibodies and associated factors in individuals with animal hoarding disorder (AHD) and their dogs in Curitiba, Southern Brazil. Blood samples were obtained from 264 dogs (21 households) and 19 individuals with AHD (11 households). Their blood was tested by indirect fluorescent antibody test (IFAT). Overall, anti-Toxoplasma gondii seropositivity was found in 21/264 dogs (7.95%; 95% CI: 4.69-11.22) with titers ranging from 16 to 4096, and in 7/19 individuals with AHD (36.84%; CI: 15.15-58.53) with titers ranging from 16 to 64. Serological analysis for anti-T. gondii antibodies were considered positive in at least one individual or dog in 9/11 (81.82%; 95% CI: 59.03-100.00) cases that were thoroughly assessed. Surprisingly, the seropositivity of individuals with AHD and their dogs was among the lowest reportedly observed in human and dog populations of Brazil. There was no significant association between positive owners and positive dogs or the presence of cats in the household. Regard epidemiological variables, a significant association was found between dog's seropositivity and the type of dog food. To the authors' knowledge, the present study represents the first investigation of T. gondii seroprevalence in individuals with hoarding disorder and their dogs. In conclusion, despite low sanitary conditions, anti-Toxoplasma gondii antibodies frequency in individuals with AHD and their dogs are lower than the general population likely due to low protozoan load in such isolated households.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/epidemiologia , Transtorno de Acumulação/epidemiologia , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Ração Animal , Animais , Brasil/epidemiologia , Doenças do Cão/sangue , Doenças do Cão/imunologia , Cães , Geografia Médica , Colecionismo/sangue , Colecionismo/epidemiologia , Colecionismo/imunologia , Transtorno de Acumulação/sangue , Transtorno de Acumulação/imunologia , Humanos , Estudos Soroepidemiológicos , Análise Espacial , Toxoplasmose/sangue , Toxoplasmose/imunologia
18.
Aust Vet J ; 98(8): 380-387, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32350856

RESUMO

OBJECTIVE: The aim of this study was to utilise wild rabbits (Oryctolagus cuniculus) as a sentinel species to study levels of environmental contamination with N. caninum and T. gondii in South Australia, and to examine associations with rainfall, climate and land use. DESIGN: Toxoplasma gondii (T. gondii), an apicomplexan parasite, causes the clinical disease toxoplasmosis, which can affect sheep as well as humans and many other animals. Neosporosis, the clinical disease caused by closely related Neospora caninum (N. caninum), causes abortions in cattle, with large economic impacts to cattle industries. METHODS: Aliquots of wild rabbit (Oryctolagus cuniculus) serum were obtained from twelve sites across South Australia over a period of eighteen years, with a total of 2114 samples. An in-house Modified Agglutination Test (MAT) was developed, and samples were screened for the specific antibodies against both T.gondii and N. caninum. RESULTS: Overall, 9.9% of samples screened for T. gondii tested positive and 6.1% of samples screened for N. caninum tested positive. There was no difference observed in seroprevalence of T.gondii specific antibodies between samples collected throughout summer, autumn, winter or spring. By contrast, a significantly higher (p=0.030) seroprevalence of N. caninum specific antibodies was observed in spring than any other season. T. gondii and N. caninum antibodies were discovered at sites across a broad area of South Australia, indicating these environments maybe infected with both parasites. CONCLUSION: Results provide evidence that suggests N. caninum oocysts may have different survival characteristics, such as varying tolerances to low relative humidity, than T. gondii oocysts.


Assuntos
Doenças dos Bovinos , Coccidiose/veterinária , Neospora/imunologia , Doenças dos Ovinos , Toxoplasma/imunologia , Toxoplasmose Animal , Aborto Animal , Animais , Anticorpos Antiprotozoários , Bovinos , Feminino , Humanos , Gravidez , Coelhos , Espécies Sentinelas , Estudos Soroepidemiológicos , Ovinos , Austrália do Sul
19.
BMC Public Health ; 20(1): 766, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448258

RESUMO

BACKGROUND: Findings on the association between Toxoplasma gondii (T. gondii) infection and suicide are contradictory. This paper aimed to resolve this uncertainty by conducting a meta-analysis. METHODS: We found the relevant studies using keywords include "Toxoplasmosis" and "Suicide" and the related synonyms in international databases such as ISI, Medline, and Scopus. The eligible studies were included in the meta-analysis phase. The random effect approach was applied to combine the results. RESULTS: Out Of 150 initial studies, 15 were included in the meta-analysis. Odds of suicide in people with T. gondii infection was 43% (OR: 1.43, 95%CI; 1.15 to 1.78) higher than those without this infection. The test for publication bias was not statistically significant, which indicates the absence of likely publication bias. CONCLUSION: This study confirms that T. gondii infection is a potential risk factor for suicide. To reduce cases of suicide attributable to T. gondii infection, it is recommended to implement some measures to prevent and control the transmission of the disease.


Assuntos
Suicídio , Toxoplasmose/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Toxoplasma/imunologia , Adulto Jovem
20.
Korean J Parasitol ; 58(2): 185-189, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32418388

RESUMO

Immunogenicity of dendritic cell-derived exosomes stimulated with Toxoplasma gondii lysates (TLA exo), mixed with cholera toxin as an adjuvant, was investigated in mice immunized via 2 mucosal routes (ocular vs intranasal). BALB/c mice were injected 3 times with TLA exo vaccine at 2 week interval, and the levels of IgG in serum and IgA in tear, saliva, feces, and vaginal wash were measured. To observe the expression of T. gondii-specific B1 gene, mice infected with ME49 T. gondii cysts were immunized with TLA exo or PBS exo (not stimulated with TLA), and their brain tissues were examined. The mice vaccinated via intranasal route elicited significantly higher humoral and mucosal immune responses compared with mice treated with PBS alone. Also, mice immunized via ocular route (by eyedrop) induced significantly higher T. gondii-specific IgG in serum and IgA in tear and feces in comparison with PBS controls. B1 gene expression was significantly lower in TLA exo vaccinated mice than in PBS or PBS exo vaccinated mice. These results demonstrated that ocular immunization of mice with TLA exo vaccine has the potential to stimulate systemic or local antibody responses. This study also highlighted an advantage of an eyedrop vaccine as an alternative for T. gondii intranasal vaccines.


Assuntos
Células Dendríticas/imunologia , Exossomos/imunologia , Olho/imunologia , Toxoplasma/imunologia , Animais , Camundongos Endogâmicos BALB C , Toxoplasma/genética
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