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1.
Front Immunol ; 12: 727457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804013

RESUMO

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler's virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 - 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.


Assuntos
Infecções Bacterianas/genética , Toxoplasmose/genética , Viroses/genética , Adolescente , Anticorpos Antibacterianos/sangue , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Bactérias/imunologia , Infecções Bacterianas/sangue , Infecções Bacterianas/imunologia , Caseínas/genética , Caseínas/imunologia , Criança , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Humanos , Estudos Longitudinais , Polimorfismo de Nucleotídeo Único , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Toxoplasma/imunologia , Toxoplasmose/sangue , Toxoplasmose/imunologia , Viroses/sangue , Viroses/imunologia , Vírus/imunologia
2.
PLoS Pathog ; 17(10): e1009970, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34597344

RESUMO

Toxoplasma gondii is an orally acquired pathogen that induces strong IFN-γ based immunity conferring protection but that can also be the cause of immunopathology. The response in mice is driven in part by well-characterized MyD88-dependent signaling pathways. Here we focus on induction of less well understood immune responses that do not involve this Toll-like receptor (TLR)/IL-1 family receptor adaptor molecule, in particular as they occur in the intestinal mucosa. Using eYFP-IL-12p40 reporter mice on an MyD88-/- background, we identified dendritic cells, macrophages, and neutrophils as cellular sources of MyD88-independent IL-12 after peroral T. gondii infection. Infection-induced IL-12 was lower in the absence of MyD88, but was still clearly above noninfected levels. Overall, this carried through to the IFN-γ response, which while generally decreased was still remarkably robust in the absence of MyD88. In the latter mice, IL-12 was strictly required to induce type I immunity. Type 1 and type 3 innate lymphoid cells (ILC), CD4+ T cells, and CD8+ T cells each contributed to the IFN-γ pool. We report that ILC3 were expanded in infected MyD88-/- mice relative to their MyD88+/+ counterparts, suggesting a compensatory response triggered by loss of MyD88. Furthermore, bacterial flagellin and Toxoplasma specific CD4+ T cell populations in the lamina propria expanded in response to infection in both WT and KO mice. Finally, we show that My88-independent IL-12 and T cell mediated IFN-γ production require the presence of the intestinal microbiota. Our results identify MyD88-independent intestinal immune pathways induced by T. gondii including myeloid cell derived IL-12 production, downstream type I immunity and IFN-γ production by ILC1, ILC3, and T lymphocytes. Collectively, our data reveal an underlying network of immune responses that do not involve signaling through MyD88.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas/imunologia , Subunidade p40 da Interleucina-12/imunologia , Toxoplasmose Animal/imunologia , Animais , Mucosa Intestinal/imunologia , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/deficiência , Receptores Toll-Like/imunologia , Toxoplasma/imunologia
3.
Parasit Vectors ; 14(1): 508, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583758

RESUMO

BACKGROUND: Latent toxoplasmosis, i.e. a lifelong infection with the protozoan parasite Toxoplasma gondii, affects about a third of the human population worldwide. In the past 10 years, numerous studies have shown that infected individuals have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases. METHODS: A cross-sectional internet study was performed on a population of 4499 (786 Toxoplasma-infected) participants and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of COVID-19. RESULTS: Logistic regression and partial Kendall correlation controlling for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1.50) before sport (OR = 1.30) and borreliosis (1.27). It also had the strongest effect on the risk of severe course of infection (Tau = 0.146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat-keeping on higher likelihood of COVID infection and higher severity of the course of infection because the effect of cat-keeping was also observed (and in particular) in a subset of Toxoplasma-infected respondents (Tau = 0.153). Effects of keeping a cat were detected only in respondents from multi-member families, suggesting that a cat could be a vector for the transmission of SARS-CoV-2 within a family. CONCLUSIONS: Toxoplasmosis is currently not considered a risk factor for COVID-19, and Toxoplasma-infected individuals are neither informed about their higher risk nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on COVID-19-associated effects on public health could be considerable.


Assuntos
COVID-19/epidemiologia , COVID-19/parasitologia , Mídias Sociais , Toxoplasma/patogenicidade , Toxoplasmose/complicações , COVID-19/fisiopatologia , Estudos Transversais , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Índice de Gravidade de Doença , Eslováquia/epidemiologia , Inquéritos e Questionários , Toxoplasma/imunologia
4.
Front Immunol ; 12: 726615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512659

RESUMO

Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan that can cause serious public health problems. However, there is no effectively preventive or therapeutic strategy available for human and animals. In the present study, we developed a DNA vaccine encoding T. gondii oxidoreductase from short-chain dehydrogenase/reductase family (TgSDRO-pVAX1) and then entrapped in chitosan and poly lactic-co-glycolic acid (PLGA) to improve the efficacy. When encapsulated in chitosan (TgSDRO-pVAX1/CS nanospheres) and PLGA (TgSDRO-pVAX1/PLGA nanospheres), adequate plasmids were loaded and released stably. Before animal immunizations, the DNA vaccine was transfected into HEK 293-T cells and examined by western blotting and laser confocal microscopy. Th1/Th2 cellular and humoral immunity was induced in immunized mice, accompanied by modulated secretion of antibodies and cytokines, promoted the maturation and MHC expression of dendritic cells, and enhanced the percentages of CD4+ and CD8+ T lymphocytes. Immunization with TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres conferred significant immunity with lower parasite burden in the mice model of acute toxoplasmosis. Furthermore, our results also lent credit to the idea that TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres are substitutes for each other. In general, the current study proposed that TgSDRO-pVAX1 with chitosan or PLGA as the delivery vehicle is a promising vaccine candidate against acute toxoplasmosis.


Assuntos
Antígenos de Protozoários/administração & dosagem , Quitosana/administração & dosagem , Nanosferas/administração & dosagem , Oxirredutases/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Proteínas de Protozoários/administração & dosagem , Vacinas Protozoárias/administração & dosagem , Toxoplasmose Animal/prevenção & controle , Vacinas de DNA/administração & dosagem , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Células Dendríticas/imunologia , Feminino , Células HEK293 , Humanos , Imunoglobulina G/imunologia , Linfócitos/imunologia , Camundongos Endogâmicos BALB C , Oxirredutases/genética , Plasmídeos , Proteínas de Protozoários/genética , Ratos Sprague-Dawley , Toxoplasma/imunologia
5.
Int J Food Microbiol ; 356: 109333, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399305

RESUMO

Toxoplasmosis is a globally spread disease, affecting humans and many animal species, including birds. Antibodies to Toxoplasma gondii were detected in ostriches from South and North America, Africa and Asia. Except for one study from Spain, there is a lack of information about T. gondii seroprevalence in ostriches from Europe. For this reason, the aim of the study was to detect antibodies to T. gondii in farm-reared ostriches from the Czech Republic. Serum samples of 409 ostriches (Struthio camelus), collected at 9 farms were tested by Latex agglutination test. Antibodies to T. gondii were detected in 149 (36%) birds with a statistical difference for individual farms (8%-71%, p = 0.0121), and regions (8%-65%, p = 0.002). Seropositivity did not statistically differ (p > 0.05) in size of farms (50% and 35% on small and large farms, respectively), sex of birds (38% and 35% in males and females, respectively), season and year of collection. Tissue samples (brain, heart, and pectoral muscle) of 105 birds were also tested by PCR to detect T. gondii DNA. The parasite T. gondii was detected in the brain and heart of one seronegative ostrich (1%) from a small farm. Based on our results, we can assume that ostriches may present high risk of toxoplasmosis for humans through consumption of raw or undercooked ostrich meat and even seronegative individuals could harbor T. gondii in their tissues. To our knowledge, this is the first serological detection of T. gondii in ostriches in the Czech Republic, and the first PCR detection in Europe.


Assuntos
Struthioniformes , Toxoplasma , Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários/sangue , República Tcheca , DNA de Protozoário/análise , Fazendas , Feminino , Humanos , Masculino , Fatores de Risco , Struthioniformes/sangue , Struthioniformes/parasitologia , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose Animal/sangue , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/epidemiologia
6.
Sci Rep ; 11(1): 17207, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446779

RESUMO

Toxoplasma gondii is a globally wide-spread parasite that infects almost all species of mammals and birds, including humans. We studied the spatial distribution of individual T. gondii-seropositive wild boar in Gifu Prefecture (10,621 km2), Japan. Altogether, 744 wild boars were captured at 663 points around human settlements in Gifu Prefecture. Serum samples were collected after recording the exact capture locations, along with each wild boar's body length and sex. We then used a commercial enzyme-linked immunosorbent assay kit for swine to measure anti-T. gondii antibodies in these animals. Among the 744 wild boars, 169 tested positive for T. gondii (22.7%). No significant difference in T. gondii seroprevalence was observed between the mountainous northern region with high winter snow cover and the mild-wintered geographical plain of the southern part of the prefecture. In contrast, 8 of the 11 wild boars that were captured in a public park surrounded by residential areas showed T. gondii seropositivity (72.7%), a value significantly higher than those of the wild boar populations in the other prefecture areas. This in-depth analysis, which spans the big city suburbs and rural areas of a whole prefecture, explains the seroprevalence of zoonotic T. gondii in wild boar and has public health implications.


Assuntos
Anticorpos Antiprotozoários/imunologia , Doenças dos Suínos/diagnóstico , Toxoplasma/imunologia , Toxoplasmose Animal/diagnóstico , Animais , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Geografia , Japão/epidemiologia , Masculino , Estudos Soroepidemiológicos , Sus scrofa/classificação , Sus scrofa/parasitologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/parasitologia , Toxoplasma/fisiologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia , Zoonoses/parasitologia
7.
Front Immunol ; 12: 643292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262559

RESUMO

Toxoplasmosis is a prevalent parasitic disease caused by Toxoplasma gondii (T. gondii). Under the control of the host immune system, T. gondii persists as latent bradyzoite cysts. Immunosuppression leads to their reactivation, a potentially life-threatening condition. Interferon-gamma (IFN-γ) controls the different stages of toxoplasmosis. Here, we addressed the role of the parasite surface antigen P18, belonging to the Surface-Antigen 1 (SAG-1) Related Sequence (SRS) family, in a cyst-forming strain. Deletion of P18 gene (KO P18) impaired the invasion of parasites in macrophages and IFN-γ-mediated activation of macrophages further reduced the invasion capacity of this KO, as compared to WT strain. Mice infected by KO P18, showed a marked decrease in virulence during acute toxoplasmosis. This was consequent to less parasitemia, accompanied by a substantial recruitment of dendritic cells, macrophages and natural killer cells (NK). Furthermore, KO P18 resulted in a higher number of bradyzoite cysts, and a stronger inflammatory response. A prolonged survival of mice was observed upon immunosuppression of KO P18 infected BALB/c mice or upon oral infection of Severe Combined Immunodeficiency (SCID) mice, with intact macrophages and natural killer (NK) cells. In stark contrast, oral infection of NSG (NOD/Shi-scid/IL-2Rγnull) mice, defective in macrophages and NK cells, with KO P18, was as lethal as that of the control strain showing that the conversion from bradyzoites to tachyzoites is intact and, suggesting a role of P18 in the response to host IFN-γ. Collectively, these data demonstrate a role for P18 surface antigen in the invasion of macrophages and in the virulence of the parasite, during acute and chronic toxoplasmosis.


Assuntos
Células Dendríticas/imunologia , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Toxoplasma , Toxoplasmose , Fatores de Virulência , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos SCID , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/genética , Toxoplasmose/imunologia , Fatores de Virulência/genética , Fatores de Virulência/imunologia
8.
Vet Parasitol ; 296: 109515, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34242913

RESUMO

The present study aimed to compare different indirect and direct diagnostic techniques to diagnose Toxoplasma gondii in free-range chickens. Samples of 386 chickens obtained from 24 Paraná properties were used for serological analysis by indirect fluorescent antibody test (IFAT), modified agglutination test (MAT), and enzyme-linked immunosorbent assay (ELISA). Animals positive by IFAT and/or MAT had their tissues submitted to the mouse bioassay, and those who were positive in this technique had their blood, tissues, and acidic pepsin tissue digestion submitted to PCR (conventional, nested, and quantitative-PCR (qPCR)). One hundred and nineteen chickens (30.8 %) were positive in at least one of the serological tests, being 102 (26.4 %) in the IFAT, 64 (16.6 %) in the MAT, and 62 (16.0 %) in the ELISA. The IFAT was used as a gold standard, and the MAT showed higher sensitivity (46.0 %) and specificity (94.0) compared to ELISA (43.5 % and 93.6 %, respectively). Ninety samples of eighteen chickens positive in the mouse bioassay were subjected to PCR, and according to molecular tests, the conventional PCR detected the T. gondii DNA in 30 % (27/90) of the samples, in 38.8 % (35/90) with nested-PCR and 40.0 % (36/90) with real-time. According to molecular analyzes, the sensitivity was higher in ITS1 nested-PCR (69.4 %) and specificity in conventional PCR-529bp (90.7 %), using the qPCR as the gold standard. MAT and ELISA had similarities in concordance analyzes. The IFAT was the serological technique with the highest agreement with the mouse bioassay, and serological tests in parallel showed to be a good screening option for the isolation of T. gondii in chick tissues. The PCR markers effectively detected the parasite DNA, and the heart was the tissue with the highest number of positives samples. The conventional PCR had sensitivity similar to nested-PCR and qPCR and could be a cheaper alternative to diagnose T. gondii infection in chicken tissues.


Assuntos
Anticorpos Antiprotozoários , Galinhas , Doenças das Aves Domésticas , Toxoplasma , Toxoplasmose Animal , Testes de Aglutinação/veterinária , Animais , Anticorpos Antiprotozoários/sangue , Bioensaio/veterinária , Galinhas/parasitologia , Marcadores Genéticos/genética , Camundongos , Doenças das Aves Domésticas/diagnóstico , Testes Sorológicos/veterinária , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose Animal/diagnóstico
9.
Parasitol Res ; 120(8): 2897-2903, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34313806

RESUMO

A cross-sectional study was carried out to determine the seroprevalence of Toxoplasma gondii and associated risk factors in pigs in the largest pork-producing region in Cuba. Serum samples from 420 pigs, including 210 sows and 210 post-weaning pigs, were tested for antibodies against T. gondii using a commercial indirect enzyme-linked immunosorbent assay. Anti-T. gondii antibodies were detected in 56 animals (13.3%, 95% CI: 10.1-16.6). A generalized estimating equations model revealed that the risk factors associated with higher seropositivity in pigs were altitude (higher in farm's location < 250 m above sea level (masl) versus ≥ 250 masl) and age (higher in sows compared to post-weaning pigs). The results indicated that this protozoan parasite is widely distributed on pig farms in the study area, which is a public health concern since the consumption of raw or undercooked pork meat products containing tissue cysts is considered one of the main routes of T. gondii transmission worldwide. Control measures should be implemented to reduce the risk of exposure to T. gondii in pigs in Cuba.


Assuntos
Sus scrofa/parasitologia , Doenças dos Suínos , Toxoplasma , Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários , Estudos Transversais , Cuba/epidemiologia , Feminino , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia
10.
Ann Agric Environ Med ; 28(2): 237-242, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184504

RESUMO

INTRODUCTION AND OBJECTIVE: Toxoplasmosis is an important zoonosis caused by a protozoan, Toxoplasma gondii. Raw or undercooked venison may be a source of infection in humans. The aim of the study was to determine the prevalence of T. gondii antibodies in wild boar from the Strzalowo Forest Division of the Warmia and Mazury Region of Poland. MATERIAL AND METHODS: A total of 90 samples were collected from 50 wild boar: 40 from both tongue and diaphragm muscles, 4 from diaphragm muscles and six from tongue muscles. Samples were analyzed using the commercial PrioCHECK® Toxoplasma Ab porcine ELISA, according to the manufacturer's instructions. RESULTS: T. gondii antibodies were detected in 24 of 50 (48%) tested animals. T. gondii antibodies were detected in 40 of 90 (44.4%) tested samples (21 of tongue muscles and 19 of diaphragm muscles). In the 40 wild boar that provided samples of meat juice from the tongue and diaphragm muscles, specific antibodies were more prevalent in the tongue (20 of 40 animals - 50%) than in the diaphragm muscles (17 of 40 animals - 42.5%). CONCLUSIONS: The study revealed a high percentage of wild boar seropositive to T. gondii. Muscle samples to obtain meat juice are easily available and simple to collect, even on the hunting grounds, which makes them suitable material for detecting T. gondii antibodies in wild boar. Wild boar are essential to T. gondii circulation in the environment, and raw or undercooked venison may be a source of human infections with this parasite.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças dos Suínos/sangue , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/sangue , Animais , Florestas , Polônia/epidemiologia , Estudos Soroepidemiológicos , Sus scrofa , Suínos , Doenças dos Suínos/epidemiologia , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia
11.
Parasitol Res ; 120(7): 2303-2309, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110502

RESUMO

Toxoplasma gondii is an intracellular protozoan parasite that can remarkably infect, survive, and replicate in almost all mammalian cells and can cause severe neurological and ocular damage in immunocompromised individuals. It is known that Natural Killer cells (NK cells), as a type of cytotoxic lymphocyte, have critical protective roles in innate immunity during the T. gondii infection through releasing interferon gamma (IFN-γ). Interleukin 12 (IL-12) is a pivotal critical cytokine for the generation of IFN-γ-producing NK cells. Several studies have shown cytokines' impact on NK cell activation; and IL-2 has an important role with a potent stimulatory factor for NK cells. In this review, we summarized the mechanism of interleukin-12 production stimulation by T. gondii tachyzoites and discussed several factors affecting this mechanism.


Assuntos
Interleucina-12/fisiologia , Células Matadoras Naturais/imunologia , Toxoplasma/fisiologia , Toxoplasmose/imunologia , Animais , Humanos , Imunidade Inata , Hospedeiro Imunocomprometido , Interferon gama/imunologia , Interferon gama/metabolismo , Toxoplasma/imunologia
12.
Nat Commun ; 12(1): 3842, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158487

RESUMO

Toxoplasma gondii is hypothesized to manipulate the behavior of warm-blooded hosts to promote trophic transmission into the parasite's definitive feline hosts. A key prediction of this hypothesis is that T. gondii infections of non-feline hosts are associated with costly behavior toward T. gondii's definitive hosts; however, this effect has not been documented in any of the parasite's diverse wild hosts during naturally occurring interactions with felines. Here, three decades of field observations reveal that T. gondii-infected hyena cubs approach lions more closely than uninfected peers and have higher rates of lion mortality. We discuss these results in light of 1) the possibility that hyena boldness represents an extended phenotype of the parasite, and 2) alternative scenarios in which T. gondii has not undergone selection to manipulate behavior in host hyenas. Both cases remain plausible and have important ramifications for T. gondii's impacts on host behavior and fitness in the wild.


Assuntos
Anticorpos Antiprotozoários/imunologia , Gatos/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Animais , Comportamento Animal , Gatos/parasitologia , Gatos/fisiologia , Feminino , Interações Hospedeiro-Parasita , Masculino , Toxoplasma/fisiologia , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/parasitologia
13.
Parasitol Res ; 120(8): 2855-2861, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185155

RESUMO

This study aimed to compare the immune response against Toxoplasma gondii (T. gondii) in BALB/c mice induced by excreted/secreted (E/S) antigens and mannose-modified nanoliposome of E/S antigens. Here, E/S antigens and mannose-modified nanoliposome of E/S antigens were firstly prepared, and then BALB/c female inbred mice were separately immunized. In the next step, anti-E/S antigen antibodies and the relative expression levels of IL-10 and IL-12 mRNA were detected by ELISA and real-time PCR, respectively. After immunization, mice were intraperitoneally challenged with 102 tachyzoites of T. gondii, and the survival rate was recorded. The ELISA analysis showed significant differences between the levels of anti-E/S antigen antibodies in the mice immunized by E/S antigens and those immunized by mannose-modified nanoliposome of E/S antigens at days 7, 10, 20, 25, and 30 (P < 0.05). Real-time PCR analysis showed that the relative expression of IL-10 was significantly decreased during 20 days. Yet, the relative expression of IL-12 was significantly increased during 20 days (P < 0.05). In T. gondii challenge test, significant differences were found between the survival rates of mice immunized by E/S antigens and mice immunized by mannose-modified nanoliposome with E/S antigens. This project evidenced that mannose-modified nanoliposome of E/S antigens induced a more powerful immune response against T. gondii in BALB/c mice when compared with excreted/secreted antigens alone.


Assuntos
Vacinas Protozoárias , Toxoplasma , Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários , Antígenos de Protozoários/imunologia , Feminino , Imunidade Humoral , Interleucina-10 , Interleucina-12 , Lipossomos , Manose , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Proteínas de Protozoários , Vacinas Protozoárias/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia
14.
Sci Rep ; 11(1): 12709, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135407

RESUMO

Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-ß1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.


Assuntos
Vilosidades Coriônicas/parasitologia , Ciclo-Oxigenase 2/metabolismo , Gotículas Lipídicas/metabolismo , Toxoplasma/crescimento & desenvolvimento , Trofoblastos/parasitologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Vilosidades Coriônicas/imunologia , Vilosidades Coriônicas/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Interações Hospedeiro-Parasita , Humanos , Interleucinas/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Nitritos/metabolismo , Toxoplasma/imunologia , Fator de Crescimento Transformador beta/metabolismo , Trofoblastos/imunologia , Trofoblastos/metabolismo
15.
Vet Parasitol ; 296: 109497, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147768

RESUMO

Toxoplasmosis is a worldwide zoonosis caused by the obligate intracellular apicomplexan parasite Toxoplasma gondii (T. gondii). Chickens are ground-feeders and represent, especially if free-range, important intermediate hosts in the epidemiology of toxoplasmosis and are used as sentinels of environmental contamination with T. gondii oocysts. Until now, little is known about the burden and regional distribution of T. gondii cysts in the chicken brain. It was therefore the aim of this study to investigate the abundance and specific distribution of T. gondii cysts within the chicken brain following chronic infection with a type II strain (76 K) of T. gondii. A total of 29 chickens were included in the study and divided into control group (n = 9) and two different infection groups, a low dose (n = 10) and a high dose (n = 10) group, which were orally inoculated with 1500 or 150,000 T. gondii oocysts per animal, respectively. Seroconversion was detected in the majority of chickens of the high dose group, but not in the animals of the low dose and the control group. Moreover, T. gondii DNA was detected most frequently in the brain and more frequently in the heart than in liver, spleen, thigh and pectoral muscle using qPCR analysis. The number of T. gondii cysts, quantified in the chicken brain using histological analysis, seems to be considerably lower as compared to studies in rodents, which might explain why T. gondii infected chickens very rarely, if at all, develop neurological deficits. Similar to observations in mice, in which no lateralisation for T. gondii cysts was reported, T. gondii cysts were distributed nearly equally between the left and right chicken brain hemispheres. When different brain regions (fore-, mid- and hindbrain) were compared, all T. gondii cysts were located in the forebrain with the overwhelming majority of these cysts being present in the telencephalic pallium and subpallium. More studies including different strains and higher doses of T. gondii are needed in order to precisely evaluate its cyst burden and regional distribution in the chicken brain. Together, our findings provide insights into the course of T. gondii infection in chickens and are important to understand the differences of chronic T. gondii infection in the chicken and mammalian brain.


Assuntos
Cistos , Doenças das Aves Domésticas , Toxoplasma , Toxoplasmose Animal , Animais , Encéfalo/parasitologia , Galinhas/parasitologia , Efeitos Psicossociais da Doença , Cistos/parasitologia , Cistos/veterinária , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/patologia , Toxoplasma/imunologia , Toxoplasmose Animal/parasitologia
16.
Rev Bras Ginecol Obstet ; 43(5): 351-356, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34077987

RESUMO

OBJECTIVE: Most prenatal screening programs for toxoplasmosis use immunoassays in serum samples of pregnant women. Few studies assess the accuracy of screening tests in dried blood spots, which are of easy collection, storage, and transportation. The goals of the present study are to determine the performance and evaluate the agreement between an immunoassay of dried blood spots and a reference test in the serum of pregnant women from a population-based prenatal screening program for toxoplasmosis in Brazil. METHODS: A cross-sectional study was performed to compare the immunoassays Imunoscreen Toxoplasmose IgM and Imunoscreen Toxoplasmose IgG (Mbiolog Diagnósticos, Ltda., Contagem, Minas Gerais, Brazil)in dried blood spots with the enzyme-linked fluorescent assay (ELFA, BioMérieux S.A., Lyon, France) reference standard in the serum of pregnant women from Minas Gerais Congenital Toxoplasmosis Control Program. RESULTS: The dried blood spot test was able to discriminate positive and negative results of pregnant women when compared with the reference test, with an accuracy of 98.2% for immunoglobulin G (IgG), and of 95.8% for immunoglobulin M (IgM). CONCLUSION: Dried blood samples are easy to collect, store, and transport, and they have a good performance, making this a promising method for prenatal toxoplasmosis screening programs in countries with continental dimensions, limited resources, and a high prevalence of toxoplasmosis, as is the case of Brazil.


Assuntos
Teste em Amostras de Sangue Seco/métodos , Técnicas Imunoenzimáticas/métodos , Toxoplasma/isolamento & purificação , Toxoplasmose Congênita/diagnóstico , Toxoplasmose/diagnóstico , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Programas de Rastreamento , Vigilância da População , Gravidez , Gestantes , Diagnóstico Pré-Natal , Prevalência , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Toxoplasmose Congênita/epidemiologia
17.
mBio ; 12(3): e0133121, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34154412

RESUMO

Toxoplasmic encephalitis can develop in individuals infected with the protozoan parasite Toxoplasma gondii and is typified by parasite replication and inflammation within the brain. Patients often present with seizures, but the parasite genes and host pathways involved in seizure development and/or propagation are unknown. We previously reported that seizure induction in Toxoplasma-infected mice is parasite strain dependent. Using quantitative trait locus mapping, we identify four loci in the Toxoplasma genome that potentially correlate with seizure development. In one locus, we identify the polymorphic virulence factor, GRA15, as a Toxoplasma gene associated with onset of seizures. GRA15 was previously shown to regulate host NF-κB-dependent gene expression during acute infections, and we demonstrate a similar role for GRA15 in brains of toxoplasmic encephalitic mice. GRA15 is important for increased expression of interleukin 1 beta (IL-1ß) and other IL-1 pathway host genes, which is significant since IL-1 signaling is involved in onset of seizures. Inhibiting IL-1 receptor signaling reduced seizure severity in Toxoplasma-infected mice. These data reveal one mechanism by which seizures are induced during toxoplasmic encephalitis. IMPORTANCE Inflammation in the brain caused by infections lead to seizures and other neurological symptoms. But the microbial products that induce seizures as well as the host pathways downstream of these factors are largely unknown. Using a nonbiased genetic screening approach, we identify 4 loci in the Toxoplasma genome that correlate with the induction of seizures in Toxoplasma-infected mice. One of these loci contains the gene, GRA15, which we demonstrate is associated with seizure development in toxoplasmic encephalitic mice. GRA15 accomplishes this in part by activating host pathways that lead to increased IL-1 receptor signaling and that inhibition of this signaling inhibits Toxoplasma-induced seizures.


Assuntos
Encéfalo/imunologia , Interações Hospedeiro-Parasita/imunologia , Interleucina-1beta/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Transdução de Sinais/imunologia , Toxoplasma/genética , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Feminino , Expressão Gênica , Genoma de Protozoário , Humanos , Interleucina-1beta/genética , Camundongos , Camundongos Endogâmicos C57BL , Convulsões/imunologia , Convulsões/parasitologia , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Toxoplasmose Animal/parasitologia , Fatores de Virulência
18.
PLoS One ; 16(6): e0245572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34086692

RESUMO

The protozoan parasite, Toxoplasma gondii is estimated to infect one-third of the world's population. Infection in pregnant women can cause severe conditions for their babies. Until now, there is no data regarding Toxoplasma infection from Makassar pregnant mothers. This study aims to obtain information on Toxoplasma specific antibodies and to measure the risk factor associate with parasite infection. This cross-sectional study conducted in 9 of 47 primary health centres (Puskesmas) in Makassar. Blood samples and questionnaires were collected from 184 pregnant women aged 15-42 years old from September to October 2020. ELISA technique was used to examine the IgG and IgM antibodies. Univariable and multivariable analyses were carried out to measure factors that independently associate with Toxoplasma antibody positivity. Our result showed the range of Toxoplasma IgM and IgG are 0.06-1.01 and 0.09-3.01, respectively. While no one of our participants has an acute Toxoplasma gondii infection (IgM positive), we found 32,6% pregnant mothers are exposed to parasite (positive IgG). Contact with cats [OR(95%CI): 10.45(3.77-28.99)], consume chicken satay [OR(95%CI): 9.72(3.71-25.48)] and consume un-boiled water/ filtered water [OR(95%CI): 5.98(1.77-20.23)] are independently associate with positive Toxoplasma IgG antibody. Based on the result, we conclude that pregnant women in Makassar are exposed to T. gondii and the oocyst and tissue cyst of parasite contaminates food and water in Makassar.


Assuntos
Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/parasitologia , Toxoplasmose/epidemiologia , Toxoplasmose/etiologia , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/imunologia , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Indonésia/epidemiologia , Mães , Gravidez , Complicações Parasitárias na Gravidez/etiologia , Complicações Parasitárias na Gravidez/imunologia , Gestantes , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Adulto Jovem
19.
Front Immunol ; 12: 606963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054794

RESUMO

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


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Interações Hospedeiro-Parasita/imunologia , Toxoplasmose Cerebral/imunologia , Toxoplasmose Congênita/imunologia , Toxoplasmose Ocular/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Feminino , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/imunologia , Hipocalcina/química , Hipocalcina/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recoverina/química , Recoverina/imunologia , Toxoplasma/imunologia , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/parasitologia , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologia , Adulto Jovem
20.
Medicine (Baltimore) ; 100(18): e25781, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950972

RESUMO

INTRODUCTION: Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn's disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment. PATIENT CONCERNS: A 56-year-old Crohn's disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors. DIAGNOSIS: Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient's genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection. INTERVENTIONS: AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient's condition gradually improved. OUTCOMES: The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health. CONCLUSION: We report a case of Crohn's disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.


Assuntos
Azatioprina/efeitos adversos , Doença de Crohn/tratamento farmacológico , Pneumonia/diagnóstico , Pirofosfatases/genética , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Azatioprina/farmacocinética , Doença de Crohn/genética , Doença de Crohn/imunologia , Análise Mutacional de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Farmacogenômicos , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/parasitologia , Polimorfismo de Nucleotídeo Único , Pirofosfatases/metabolismo , Toxoplasma/isolamento & purificação , Toxoplasmose/genética , Toxoplasmose/imunologia , Toxoplasmose/parasitologia
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