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The role of ATP during the immune system activation and protection against Plasmodium chabaudi and Plasmodium berghei infection

Grant number: 09/06652-4
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2009
Effective date (End): August 31, 2011
Field of knowledge:Biological Sciences - 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

Abstract

Malaria is responsible for one million deaths yearly, mostly affecting children. The immune system participates in the protection against Plasmodium infection, such as malaria syndromes like anemia, cerebral malaria, metabolic acidosis and systemic shock. Recently, it has been shown that innate immunity is able to detect signals such as ATP and uric acid released by damaged cells or tissues. These signs of danger appear to be important to promote the regulation of inflammation after trauma or injury caused by pathogens. However, the physiological relevance of these signals in the immune response and its mechanism are not yet clear. Recent studies suggest that P2X7 receptor recognize ATP activating the NALP3-inflamossomo complex, a set of molecules of innate immunity that controls the inflammatory caspase and induces production of IL-1b and IL-18. In malaria, it is likely that ATP could be release upon rupture of infected erythrocytes or cells of the vascular endothelium damaged by the action of effector molecules of the immune system. Thus, this project aims to assess the central role of ATP during the immune system activation and protection against P. chabaudi and P. berghei (model of cerebral malaria) infection. The project is subdivided into four sections that address specific objectives: 1) Evaluate the presence of P2X7 receptors in macrophages, dendritic cells and T and B lymphocytes of C57BL/ 6 infected mice. 2) Evaluate the parasitemia, mortality and parameters associated with the severity of the disease (body weight, temperature, anemia, cerebral malaria and respiratory syndrome) in mice deficient in P2X7 receptor and C57BL / 6 control mice. 3) Compare the activation of macrophages, dendritic cells and T and B lymphocytes in C57BL / 6 and P2X7-/ - infected mice. 4) Measure the levels of IL-1b and IL-18 in serum of C57BL / 6 andP2X7-/ - infected mice. As we shall see below, these goals are fully consistent with previous studies that have been developed by our research group with the support of FAPESP and CNPq. The outcomes in this project should contribute to the understanding of the mechanisms involved in immunity against malaria.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SALLES, Érika Machado de. Estudo do papel do ATP na ativação do sistema imune e na proteção durante a infecção por Plasmodium chabaudi.. 2011. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.

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