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Study of Toxoplasma gondii extracellular vesicles modulating the immune system of infected hosts

Abstract

Toxoplasmosis is one of the most widespread zoonoses in the world and, in some regions, 40%-70% of the population are positive for toxoplasmosis in serological tests. Around 2 billion people in the world may be infected with Toxoplasma gondii. Diagnosis can be established by the detection of anti-T. gondii antibodies; and parasite DNA by PCR in tissues/body fluids or parasite visualization in tissues. However, diagnostic tools are inefficient to demonstrate the severe infection. T. gondii secreted/excreted antigens can differentiate clinical samples from patients with cerebral toxoplasmosis from chronically infected individuals in ELISA and immunoblot. However, the molecules of these antigens that are responsible for differentiation of patient groups are not yet known. Recently, studies have shown the importance of extracellular vesicles (EVs) produced by eukaryotic and prokaryotic cells mainly in cellular communication. EVs are found in biological fluids and are involved in carrying molecules such as micro-RNAs, proteins, lipids, DNA, and others. Thus, it is gradually evident that EVs perform specialized functions and play a key role in coagulation, intercellular signaling, waste management, among others. However, the importance of EVs in the mechanism of T. gondii infection has not yet been fully elucidated. It is possible that the parasite may release different molecules via EVs into the cells and/or bloodstream of their hosts. The aim of the present project will be the study of the participation of T. gondii EVs in the stimulation of humoral and cellular immune responses in the human and murine toxoplasmosis. Initially the EVs will be purified from tachyzoites maintained in cell cultures. Next, the ability of the EVs and miRNAs to stimulate the humoral immune response of patients with symptomatic toxoplasmosis will be invested by immunological and molecular methods for the determination of possible markers. Positive sera for toxoplasmosis from patients with clinical and laboratory diagnosis of cerebral, ocular, and gestational toxoplasmosis will be used. In parallel, in the animal model will be carried out immunization tests in mice with EVs to investigate their participation in the production of inflammatory and anti-inflammatory cytokines. At the same time, the humoral response will be studied, detecting the classes of IgM antibodies and IgG subclasses (IgG1 and IgG2a) involved in the immune-protection. Next, the immunized animals will be challenged with T. gondii in order to evaluate the parasitemia and survival rates. The expected results will be important to understand the pathogen/host relationship and to evaluate the humoral and cellular immune in infected hosts, as well as the role of the EVs in the symptomatic infection. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA CRUZ, ALLECINEIA BISPO; MAIA, MARTA MARQUES; PEREIRA, INGRID DE SIQUEIRA; TANIWAKI, NOEMI NOSOMI; NAMIYAMA, GISLENE MITSUE; MAROCHI TELLES, JOAO PAULO; VIDAL, JOSE ERNESTO; JUNQUEIRA FRANCO SPEGIORIN, LIGIA COSENTINO; BRANDAO DE MATTOS, CINARA CASSIA; DE MATTOS, LUIZ CARLOS; MEIRA-STREJEVITCH, CRISTINA DA SILVA; PEREIRA-CHIOCCOLA, VERA LUCIA. Human extracellular vesicles and correlation with two clinical forms of toxoplasmosis. PLoS One, v. 15, n. 3 MAR 3 2020. Web of Science Citations: 0.
MURATA, FERNANDO HENRIQUE ANTUNES; PREVIATO, MARIANA; FREDERICO, FABIO BATISTA; BARBOSA, AMANDA PIRES; NAKASHIMA, FABIANA; DE FARIA, JR., GERALDO MAGELA; SILVEIRA CARVALHO, APARECIDA PERPETUO; MEIRA STREJEVITCH, CRISTINA DA SILVA; PEREIRA-CHIOCCOLA, VERA LUCIA; CASTIGLIONI, LILIAN; DE MATTOS, LUIZ CARLOS; SIQUEIRA, RUBENS CAMARGO; BRANDAO DE MATTOS, CINARA CASSIA. Evaluation of Serological and Molecular Tests Used for the Identification of Toxoplasma gondii Infection in Patients Treated in an Ophthalmology Clinic of a Public Health Service in Sao Paulo State, Brazil. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, FEB 7 2020. Web of Science Citations: 0.

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