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Effect of thymic atrophy induced by infection with Plasmodium berghei on the induction and development of EAE experimental

Grant number: 11/13191-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2011
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Liana Maria Cardoso Verinaud
Grantee:Rodolfo Thomé
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Thymus is the primary lymphoid organ responsible for the maturation and development of T lymphocytes, playing a primordial role in generating central tolerance. Some extrinsic factors such as infections are capable of inducing thymic atrophy. Experiments conducted in our laboratory showed that Plasmodium berghei infection causes thymic atrophy through migration of premature cells into the periphery. Malaria, caused by the protozoan Plasmodium spp, is the main infectious disease in humans. In Brazil were described over 330 thousand cases in 2010. Destruction of the parasite by T and B cell is essential for disease resolution, however there must be a subtle balance on the immune system. In this context, dendritic cells play an important role shaping T cell responses and are infected by Plasmodium in malaria acquiring immunossupressive properties. Since the relationship between infections and autoimmune diseases is not well characterized its understanding can yield therapies against a variety of chronic inflammatory autoimmune disorders, such as multiple sclerosis. Multiple sclerosis originates through the destruction of myelin that recovers the nervous termination by the immune system cells. Little is known about the factors that trigger autoimmune response, although there is accumulating evidence suggesting the involvement of infections in observations made in the main experimental model of this disease: the experimental autoimmune encephalomyelitis (EAE). T.cruzi infected mice have thymic atrophy and are known to develop autoimmune disease, Savino et al attributed the autoimmunity to the presence of immature T cells in the periphery. In this context, the main objective of this study is to evaluate whether thymic atrophy, developed in experimental infection by P.berghei, is capable to alter the predisposition and the clinical parameters of EAE in mice. It is also purpose of this project to evaluate the therapeutic potential of adoptive transfer of dendritic cells modulated with P.berghei-derived molecules in controlling EAE.

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Scientific publications (4)
(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)
THOME, RODOLFO; BOMBEIRO, ANDRE LUIS; ISSAYAMA, LUIDY KAZUO; RAPOSO, CATARINA; PINTO LOPES, STEFANIE COSTA; DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; FERREIRA, ISADORA TASSINARI; FIGUEIREDO LONGHINI, ANA LEDA; RODRIGUES OLIVEIRA, ALEXANDRE LEITE; DA CRUZ HOEFLING, MARIA ALICE; MARANHAO COSTA, FABIO TRINDADE; VERINAUD, LIANA. Exacerbation of Autoimmune Neuro-Inflammation in Mice Cured from Blood-Stage Plasmodium berghei Infection. PLoS One, v. 9, n. 10 OCT 17 2014. Web of Science Citations: 5.
THOME, RODOLFO; ISSAYAMA, LUIDY K.; DA COSTA, THIAGO ALVES; GANGI, ROSARIA D.; FERREIRA, ISADORA T.; RAPOSO, CATARINA; LOPES, STEFANIE C. P.; DA CRUZ HOEFLING, MARIA ALICE; COSTA, FABIO T. M.; VERINAUD, LIANA. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation. Immunology, v. 143, n. 2, p. 164-173, OCT 2014. Web of Science Citations: 6.
THOME, RODOLFO; ISSAYAMA, LUIDY KAZUO; DIGANGI, ROSARIA; BOMBEIRO, ANDRE LUIS; DA COSTA, THIAGO ALVES; FERREIRA, ISADORA TASSINARI; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; VERINAUD, LIANA. Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis. Immunology and Cell Biology, v. 92, n. 2, p. 124-132, FEB 2014. Web of Science Citations: 21.
THOME, RODOLFO; PINTO LOPES, STEFANIE COSTA; MARANHAO COSTA, FABIO TRINDADE; VERINAUD, LIANA. Chloroquine: Modes of action of an undervalued drug. Immunology Letters, v. 153, n. 1-2, p. 50-57, JUN 2013. Web of Science Citations: 56.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.