Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Chaves-Borges, Flávia Andrade; Souza, Maria Aparecida de; Silva, Deise A. O.; Kasper, Lloyd H.; Mineo, José Roberto

doi:10.1590/s0036-46651999000600001

Cited by 16 publications

(13 citation statements)

References 36 publications

(35 reference statements)

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“…Immune complexes detection was performed as described (Chaves-Borges et al, 1999; Barenco et al, 2014), using microtiter plates (Kartell SPA, Novigilio, Milan, Italy) coated with anti-r Tg HSP70 IgY (10 μg/mL) diluted in carbonate buffer pH 9.6 and incubated at 4°C overnight. After incubation at 37°C for 1 h, plates were washed and incubated with mouse sera diluted 1:40 in 1% PBS-TM.…”

Section: Methodsmentioning

confidence: 99%

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Czarnewski

Araújo

Oliveira

et al. 2017

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70). Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for vaccine development against toxoplasmosis.

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Section: Methodsmentioning

confidence: 99%

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Czarnewski

Araújo

Oliveira

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Conversely, oligoclonal bands against T. gondii antigens were found by Western blot in the CSF of some TE/AIDS patients, but these antibodies came from the systemic level (63). SAG1, anti‐SAG1 antibodies and immune complexes were found within the CSF of patients with toxoplasmosis, with or without concomitant HIV infection (64). More recently, the presence of specific IgA, IgM and IgG antibodies was found in the CSF of patients with TE, although it was not established if they were locally produced or traversed the blood–brain barrier (65).…”

Section: Compartmentalization Of the Antibody Responsementioning

confidence: 99%

Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host

Correa

Cañedo-Solares

Ortiz-Alegría

et al. 2007

Parasite Immunology

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The apicomplexan parasite Toxoplasma gondii is remarkable in several aspects, since it is a protozoan that infects most nucleated cells in many warm-blooded animals, worldwide. Although the cellular immune response against T. gondii is critical for infection control, antibodies may either enhance or block protective mechanisms, and even mediate immunological damage, directly or indirectly. Since cytokines regulate the class/subclass switch, antibodies may also be the biomarkers of protective or pathological cellular immune events. There is a scientific and clinical interest in the presence of natural and autoreactive antibodies, as well as in the 'chronic' immunoglobulin M (IgM) response and the post-treatment 'rebound'. Another interesting aspect is compartmentalization; certain immunoglobulins may uniquely be found in specific host fluids. Local synthesis has been demonstrated, but antibodies may also traverse several cell layers, like the blood-brain and haemato-ocular barriers, and the placenta. In some instances, Fc receptors (FcRs) facilitate transport and may even have a concentrator effect, which can be related to resistance or pathology. These aspects of the humoral response against T. gondii are reviewed in the present paper.

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“…Assays for the detection of T. gondii-specific antibodies are often based on crude antigen extracts (e.g., tachyzoite lysates) or purified native antigenic proteins such as the major surface antigen SAG1 (12,18,20,38). Production of these native antigens is limited, and amounts are difficult to standardize.…”

mentioning

confidence: 99%

Peptide Microarray Analysis ofIn Silico-Predicted Epitopes for Serological Diagnosis of Toxoplasma gondii Infection in Humans

Maksimov

Zerweck

Максимов

et al. 2012

Clin Vaccine Immunol

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ABSTRACTToxoplasma gondiiinfections occur worldwide in humans and animals. In immunocompromised or prenatally infected humans,T. gondiican cause severe clinical symptoms. The identification of specific epitopes onT. gondiiantigens is essential for the improvement and standardization of the serological diagnosis of toxoplasmosis. We selected 20 peptides mimicking linear epitopes on GRA1, GRA2, GRA4, and MIC3 antigenicT. gondiiproteinsin silicousing the software ABCpred. A further 18 peptides representing previously published epitopes derived from GRA1, SAG1, NTPase1, and NTPase2 antigens were added to the panel. A peptide microarray assay was established to prove the diagnostic performance of the selected peptides with human serum samples. Seropositive human serum samples (n= 184) were collected from patients presenting with acute toxoplasmosis (n= 21), latentT. gondiiinfection (n= 53), and inactive ocular toxoplasmosis (n= 10) and from seropositive forest workers (n= 100). To adjust the cutoff values for each peptide, sera from seronegative forest workers (n= 75) and patients (n= 65) were used. Univariate logistic regression suggested the significant diagnostic potential of eight novel and two previously published peptides. A test based on these peptides had an overall diagnostic sensitivity of 69% (100% in ocular toxoplasmosis patients, 86% in acutely infected patients, 81% in latently infected patients, and 57% in seropositive forest workers). The analysis of seronegative sera performed with these peptides revealed a diagnostic specificity of 84%. The results of our study suggest that the use of a bioinformatic approach for epitope prediction in combination with peptide microarray testing is a powerful method for the selection ofT. gondiiepitopes as candidate antigens for serological diagnosis.

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Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Cited by 16 publications

References 36 publications

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host

Peptide Microarray Analysis ofIn Silico-Predicted Epitopes for Serological Diagnosis of Toxoplasma gondii Infection in Humans

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