Role of molecules that signalize cellular damage in experimental malaria

• Grant number: 13/09176-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2013
• Effective date (End): August 31, 2018
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Maria Nogueira de Menezes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 15/25874-9 - Role of liver IL-1alpha in protection against superinfection during experimental malaria, BE.EP.DR

Abstract

The understanding of the immunological mechanisms in malaria is extremely important for the development of vaccines and therapeutic drugs that can give protection against the disease and its symptoms. Malaria is characterized by intense activation of the immune system that seems to contribute to protection against infection and to clinical manifestations associated with the disease. However, it is not clear which are the mechanisms responsible for the exacerbated immune response during the acute phase of infection and for the control of the disease during the chronic phase. Recently, it has been shown that innate immunity is able to detect damage signals released by injured tissues and cells as ATP, HMGB1, uric acid and IL-1±. These danger signals are called DAMPs (Danger-associated molecular patterns) and seem to be important to promote the regulation of inflammation after damage or injuries caused by pathogens, but also seem to contribute to activate the immune responses. The erythrocyte rupture and the necrosis that occurs in some organs in malaria, as liver and kidney, are conditions in which many DAMPs are released in the extracellular milieu, where they can interact with immune cells, activating them and triggering the immune response. It is known that some DAMPs play a crucial role in cell activation, for example HMGB1 is recognized by macrophages and dendritic cells and therefore leads to secretion of TNF-±, which is an important cytokine in the response to malaria. Moreover, our research group has already demonstrated that P2X7 - an ATP receptor - deficient mice show worse clinical symptoms after Plasmodium chabaudi infection, which indicates an important role for ATP in the response to infection. Thus, the objective of this project is to evaluate the role of molecules that signalize cell damage, as ATP and HMGB1, in the response to P. chabaudi infection, aiming to elucidate the immunological mechanisms involved in the DAMP response in experimental malaria. These goals are fully consistent with previous studies that have been developed by our research group with the support of FAPESP and CNPq. Expected outcomes from this project will contribute to improve the understanding of malaria immunology. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE MENEZES, MARIA NOGUEIRA; SALLES, ERIKA MACHADO; VIEIRA, FLAVIA; AMARAL, EDUARDO PINHEIRO; ZUZARTE-LUIS, VANESSA; CASSADO, ALEXANDRA; EPIPHANIO, SABRINA; ALVAREZ, JOSE MARIA; ALVES-FILHO, JOSE CARLOS; MOTA, MARIA MANUEL; et al. IL-1 alpha, promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria. SCIENTIFIC REPORTS, v. 9, MAY 20 2019. (15/20432-8, 13/09176-4, 13/07140-2, 15/25874-9)

Academic Publications

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

MENEZES, Maria Nogueira de. Role of IL-1 in experimental P. chabaudi malaria. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.