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Analysis of the modulatory role of PD-1/PD-L1 interaction in the chronic phase of the murine infection with Trypanosoma cruzi

Grant number: 14/03802-3
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2014
Effective date (End): March 31, 2018
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:José Maria Álvarez Mosig
Grantee:Raíssa Fonseca
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):15/00680-7 - Role of PD-1 pathway in TRM development and function, BE.EP.DD


Chagas disease, a human disease induced by the flagellate protozoan Trypanosoma cruzi, has no spontaneous cure, progressing to chronicity. In the chronic phase, a significant fraction of patients develop diseases of the heart and/or digestive tract, which appear to be the result of local damage induced by the parasite and immune system. It is unknown the responsible cause for the inefficiency of the immune system in the complete destruction of T. cruzi. One possibility might be immune exhaustion, a negative regulation of effector activity of parasite specific CD4+ and CD8+ cells that prevents them from mediating an efficient effector activity that results in a sterile control the parasite. In this project we intend to verify if in the chronic phase of murine infection by T. cruzi Sylvio X10/4 the PD-1/PD-L1 interaction negatively modulates the activity of effector T lymphocytes. Furthermore, we will examine if the treatment of chronic animals with monoclonal anti-PD-L1 and/or anti-PD-1 antibodies determines a decrease in parasite load and heart disease. (AU)

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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)
FONSECA, RAISSA; SALGADO, RAFAEL MOYSES; DA SILVA, HENRIQUE BORGES; DO NASCIMENTO, ROGERIO SILVA; D'IMPERIO-LIMA, MARIA REGINA; ALVAREZ, JOSE MARIA. Programmed Cell Death Protein 1-PDL1 Interaction Prevents Heart Damage in Chronic Trypanosoma cruzi Infection. FRONTIERS IN IMMUNOLOGY, v. 9, . (15/20432-8, 13/08199-0, 14/03802-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FONSECA, Raíssa. Analysis of the modulatory role of PD-1/PD-L1 interaction in the chronic phase of the murine infection with Trypanosoma cruzi.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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