MODULATION OF CARDIOMYOCYTE SIGNALING BY PRIMING WITH CITOKINES

• Grant number: 14/17586-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2014
• Effective date (End): August 31, 2016
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: José Maria Álvarez Mosig
• Grantee: Paulo César Ferreira dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chronic chagasic cardiomyopathy (CCC) is the most important morbid element of Chagas disease and its elucidation has become fundamental. Immunology studies of CCC demonstrate that the local immune response plays a dual role in the disease, acting to control the parasite but simultaneously promoting tissue injury. However, there is little information about the role of heart structural cells, such as cardiomyocytes, in the course of the disease. In other pathologies, it is known that IFN-gamma, a cytokine produced in abundance in the heart of patients with CCC, promotes the "priming" of diverse structural cell populations, positively modulating their response. Our final aim is to evaluate the role of this cytokine on the functional activity of cardiomyocytes in T. cruzi infected mice. Yet, it is not possible to directly study this subject by analyzing the heart response to the parasite in IFN-gamma-deficient mice (IFN-gammaKO or IFN-gammaRKO), since the absence of these molecules results in increased systemic parasite load that secondarily affects the heart. Thus, an alternative approach is necessary to evaluate the in vivo effect of IFN-gamma on cardiomyocytes. In this project, this is intended by studying the response of cardiac muscle cells to systemic stimulation with TLR activators, such as LPS or Poly-IC, in mice pretreated intravenously with IFN-gamma.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Paulo César Ferreira dos. Modulation of the immune signaling of cardiac cells by IFN-γ priming.. 2016. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.