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Role of purinergic receptors in the immune response development against experimental malaria

Grant number: 17/03354-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2017
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Érika Machado de Salles
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, AP.TEM

Abstract

The molecular pathways involved in activation and regulation of the immune response are important targets for studies aiming to produce vaccines and to develop new therapeutic approaches. The cells of the immune system recognize not only Pathogen-Associated Molecular Patterns (PAMPs), but also intracellular molecules named DAMPs (Damage-Associated Molecular Patterns), such as ATP, that are released in the extracellular milieu during cellular damage or stress. The detection of extracellular ATP (eATP) by purinergic receptors (P2X1-7) alerts immunological cells that trigger the inflammatory response. Some studies show that recognition of ATP by P2X7 receptors on CD4+ T lymphocytes is important for cell activation and death. Furthermore, enzymes that cleave eATP participate in the control of tissue damage and inflammation. In Malaria, an intense activation of CD4+ T cells is observed, which contributes to IFN³ production (Th1 cells), B cell activation (Tfh cells) and regulation (Treg and Tr1 cells). In addition, our research group found that the P2X7 receptor helps Th1 cell differentiation and controls the Tfh cell population during Plasmodium chabaudi infection. However, additional experiments need to be performed to complete this study. Furthermore, it is possible that other purinergic receptors are also involved in the immune response against Malaria, as well as other damage signals and their receptors. It is worth highlighting the possible role of ecto-nucleotidases (CD39 and CD73) and adenosine P1 receptors in the regulation of immune response against Malaria, with important consequences for the development of syndromes associated with severe disease. Thus, the overall objective of this project is to evaluate the role of P2X7, P1 (A2A and A2B) receptors, as well as CD39 and CD73 ecto-nucleotidases, in the development of the immune response against experimental Malaria. (AU)