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Effect of adoptive transfer of spleen cells or CD4+ T cells stimulated with ArtinM during infection with Paracoccidioides brasiliensis

Grant number: 14/16003-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Cristina Roque Antunes Barreira
Grantee:Thiago Eleutério Gonçalves
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/04088-0 - Lectin from pathogens, AP.TEM


Paracoccidioidomycosis (PCM) is caused by the fungus Paracoccidioides brasiliensis, that is dimorphism in a temperature dependent manner. The disease in humans is characterized by the transformation of the mycelial form of the fungus (infectious) to the yeast form (pathogenic). The establishment of Th1 response mediated by IL-12 is required for the development of protective immunity against PCM. In the experimental PCM, the prophylactic or therapeutic administration of ArtinM confers resistance to PCM throught of the immune response to the Th1 profile. The immunomodulatory activity induced by ArtinM promotes the protection against other intracellular pathogens, such as: Leishmania amazonensis, Leishmania major, Neospora caninum and Candida albicans. ArtinM is extracted from seeds of Artocarpus heterophyllus and exerts some biological activities: activates neutrophils, promotes the degranulation of mast cells, induces the production of IL-12 on antigen-presenting cells (APCs), activates spleen cells and CD4+ T cells. These activities result in a pattern of adequate immune response favorable to against intracellular pathogens. To investigate the contribution of lymphocytes activated by ArtinM against PCM, we propose to analyze the ability of spleen cells or CD4+ T cells after incubation with ArtinM. For this, we will realize the adoptive transfer these cells and evaluate the effect in the course of the disease. Thus, BALB/c mice will be infected with P. brasiliensis (1x106yeast/mice). After 10 days of infection, these mice will receive spleen cells or CD4+ T cells obtained from BALB/c that were stimulated ex vivo with ArtinM (625ng/mL) during 24 hours before adoptive transfer. After 30 days of infection the mice will be sacrificed and their blood and organs (spleen, liver and lung) will be collected. We will be analyzed the pro-inflammatory and anti-inflammatory cytokines in the serum and extract of the organs. Moreover, the organs will be verified by histopathology, analysis of fungal burden and quantified the frequency of granulomas. The results will be compared between the infected and non-infected mice that received by adoptive transfer the spleen cells or CD4+ T cells stimulated or not with ArtinM.

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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)
MARTINS OLIVEIRA BRITO, PATRICIA KELLEN; GONCALVES, THIAGO ELEUTERIO; FERNANDES, FABRICIO FREITAS; MIGUEL, CAMILA BOTELHO; RODRIGUES, WELLINGTON FRANCISCO; LAZO CHICA, JAVIER EMILIO; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Systemic effects in naive mice injected with immunomodulatory lectin ArtinM. PLoS One, v. 12, n. 10, . (14/16003-1, 16/23112-7, 16/10446-4, 16/04877-2, 12/09611-0, 13/04088-0)
DA SILVA, THIAGO APARECIDO; MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; GONCALVES, THIAGO ELEUTERIO; VENDRUSCOLO, PATRICIA EDIVANIA; ROQUE-BARREIRA, MARIA CRISTINA. ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 7, . (14/16003-1, 16/23112-7, 16/10446-4, 16/04877-2, 06/60642-2, 12/09611-0, 13/04088-0)

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