The heart infection by Trypanosoma cruzi: analysis of the role of cardiomyocytes in the detection of the parasite and/or tissue damage

• Grant number: 18/25984-7
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2019 - January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Maria Álvarez Mosig
• Grantee: José Maria Álvarez Mosig
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Maria Regina D'Império Lima

Abstract

In Chagas disease, a human ailment due to infection by the protozoan Trypanosoma cruzi, one third of the patients develop chronic cardiomyopathy. This pathological condition is associated with persistence of the parasite in the cardiac tissue, which is considered to be a reflex of an insufficient or inadequate local immune response. However, using a murine model of acute T. cruzi infection we have recently observed that, in addition to the infiltrating leukocytes, the cardiomyocytes play an active role in the in vivo local immune response (Santana et al., 2018). These results raise the possibility of the participation of this structural population on the cardiomyopathy present in the patients with the cardiac form of the disease.In the present project, with the long term objective to unveil the cellular and molecular elements involved in chagasic cardiomyopathy, we will study, in the heart of mice infected with T. cruzi, the in vivo role of cardiomyocytes in the detection of the parasites or local damage and the consequent signaling of the immune system.The intended studies, which give continuity to a project in my laboratory, can be grouped into two subprojects:I) Study of the role of the MyD88 adapter expressed by cardiomyocytes in the in vivo recognition of T. cruzi or the changes induced by it.II) Study of the role of the P2X7 purinergic receptor expressed by cardiomyocytes in the in vivo recognition of ATP released in the extracellular environment of cardiac tissue, as a direct or indirect result of T. cruzi infection.These studies will be addressed using induced CRE-LOX models in which the MyD88 adapter, or the P2X7 receptor, will be selectively eliminated in cardiomyocytes after treatment with tamoxifen. (AU)