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| Author(s): |
Raissa Fonseca
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2018-03-15 |
| Examining board members: |
Jose Maria Alvarez Mosig;
Niels Olsen Saraiva Câmara;
Mariana Ribeiro Dominguez;
Denise Morais da Fonseca;
José Ronnie Carvalho de Vasconcelos
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| Advisor: | Jose Maria Alvarez Mosig |
| Abstract | |
C3H/HePAS mice infected with T. cruzi Sylvio X10/4 parasites develop a chronic cardiomyopathy like the observed in human chagasic patients. Flow cytometry analysis of heart-infiltrating cells in chronically infected mice revealed higher leukocyte frequency with increased PD-1 and PD-L1 expression. In order to restore the immune response, mice were treated with anti-PD-L1 or with anti-PD-L1 and anti-PD-1, but neither exerted effects at heart pathology and parasitemia nor restored T cell response. Hence, we evaluated the possibility of using irradiated T. cruzi challenge to provide parasite antigen and co-stimulatory signaling to exhausted cells. Thus, association of anti-PD-1 and anti-PD-L1 treatment with irradiated T. cruzi challenge increased heart pathology and bradycardia as well as reduced blood parasitemia. Additionally, the treatment does not change T cell phenotype. Blocking both inhibitory interactions and provide antigen with co-stimulation seems to cause a loss in heart function despite decreasing parasitemia. (AU) | |
| FAPESP's process: | 14/03802-3 - Analysis of the modulatory role of PD-1/PD-L1 interaction in the chronic phase of the murine infection with Trypanosoma cruzi |
| Grantee: | Raíssa Fonseca |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |