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Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis

Grant number: 15/20432-8
Support type:Research Projects - Thematic Grants
Duration: December 01, 2016 - November 30, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Maria Regina D'Império Lima
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:José Maria Álvarez Mosig ; Mario Hiroyuki Hirata
Assoc. researchers:Alessandra Pontillo ; Cláudio Romero Farias Marinho ; Elena Lassounskaia ; Franklin Alan Sher ; Henrique Borges da Silva ; João Gustavo Pessini Amarante Mendes ; José Carlos Farias Alves Filho ; José Maria Álvarez Mosig ; Karina Ramalho Bortoluci ; Mario Hiroyuki Hirata ; Robson Coutinho Silva ; Sabrina Epiphanio
Associated scholarship(s):20/09043-8 - Purinergic signaling in the pathogenesis of acute lung injury and acute respiratory distress syndrome associated with pulmonary malaria, BP.PD
20/04183-6 - Evaluation of P2X7 influence on caspase-1 activation and GSDMD cleavage in Tfh and Tfr cells in experimental Malária model, BP.IC
20/01197-6 - Role of P2X7 receptor and CD39 ectonucleotidase in follicular regulatory T lymphocytes during experimental Malaria, BP.DD
+ associated scholarships 19/24700-8 - Role of P2X7 receptor on parenchymal and intravascular CD4 T cell response in a Severe Experimental Tuberculosis model, BP.DD
17/11030-9 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, BP.PD
17/03354-9 - Role of purinergic receptors in the immune response development against experimental malaria, BP.PD - associated scholarships

Abstract

Dead cells as a result of tissue damage are quickly engulfed, but before disappearing, warn the surrounding cells so that repair programs are activated. The recognition of cell damage by the innate immune system contributes to the development of inflammatory immune responses and tissue repair, but may also exacerbate tissue injuries. In some cases, uncontrolled cell death can trigger a cascade of destructive processes that ultimately amplifies tissue damage and worsens the disease prognosis. The aim of this project is to characterize the receptors of cellular damage signals that are involved in the progression of severe forms of experimental malaria and tuberculosis, seeking to interfere in these signaling pathways in order to improve disease outcomes. These infectious diseases are among the most prevalent in humans, and together account for more than one million deaths annually worldwide. Another purpose of this project is to evaluate the role of signs of damage in the development of acquired immune response during these infectious diseases. This study can bring an essential knowledge for the development of new therapeutic approaches that can be applied, in conjunction with those already used, in the treatment of severe forms of malaria and tuberculosis, as well as in other diseases (infectious or not) that are characterized by extensive tissue damage. In addition, this study may uncover new molecular mechanisms involved in the recognition of cellular damage and, therefore, increase the understanding and intervention perspectives related to these processes. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Research highlights role of molecule that directs immune response in cases of malaria 

Scientific publications (6)
(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; D'IMPERIO-LIMA, MARIA REGINA. IL-1 alpha, promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria. SCIENTIFIC REPORTS, v. 9, MAY 20 2019. Web of Science Citations: 0.
AMARAL, EDUARDO P.; DE SALLES, ERIKA MACHADO; BARBOSA BOMFIM, CAIO CESAR; SALGADO, RAFAEL MOYSES; ALMEIDA, FABRICIO M.; DE SOUZA, PAULA CAROLINA; ALVAREZ, JOSE MARIA; HIRATA, MARIO H.; LASUNSKAIA, ELENA B.; D'IMPERIO-LIMA, MARIA REGINA. Inhibiting Adenosine Receptor Signaling Promotes Accumulation of Effector CD4(+) T Cells in the Lung Parenchyma During Severe Tuberculosis. Journal of Infectious Diseases, v. 219, n. 6, p. 964-974, MAR 15 2019. Web of Science Citations: 2.
DA SILVA, HENRIQUE BORGES; DE SALLES, ERIKA MACHADO; LIMA-MAURO, ELIANA FAQUIM; SARDINHA, LUIZ ROBERTO; ALVAREZ, JOSE MARIA; D'IMPERIO LIMA, MARIA REGINA. CD28 deficiency leads to accumulation of germinal-center independent IgM(+) experienced B cells and to production of protective IgM during experimental malaria. PLoS One, v. 13, n. 8 AUG 27 2018. Web of Science Citations: 2.
FONSECA, RAISSA; SALGADO, RAFAEL MOYSES; DA SILVA, HENRIQUE BORGES; DO NASCIMENTO, ROGERIO SILVA; D'IMPERIO-LIMA, MARIA REGINA; ALVAREZ, JOSE MARIA. Programmed Cell Death Protein 1-PDL1 Interaction Prevents Heart Damage in Chronic Trypanosoma cruzi Infection. FRONTIERS IN IMMUNOLOGY, v. 9, MAY 7 2018. Web of Science Citations: 3.
DE SALLES, ERIKA MACHADO; DE MENEZES, MARIA NOGUEIRA; SIQUEIRA, RENAN; DA SILVA, HENRIQUE BORGES; AMARAL, EDUARDO PINHEIRO; CASTILLO-MENDEZ, SHEYLA INES; CUNHA, ISABELA; CASSADO, ALEXANDRA DOS ANJOS; VIEIRA, FLAVIA SARMENTO; NICHOLAS OLIVIERI, DAVID; TADOKORO, CARLOS EDUARDO; ALVAREZ, JOSE MARIA; COUTINHO-SILVA, ROBSON; D'IMPERIO-LIMA, MARIA REGINA. P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria. PLOS PATHOGENS, v. 13, n. 8 AUG 2017. Web of Science Citations: 15.
BARBOSA BOMFIM, CAIO CESAR; AMARAL, EDUARDO PINHEIRO; CASSADO, ALEXANDRA DOS ANJOS; SALLES, ERIKA MACHADO; DO NASCIMENTO, ROGERIO SILVA; LASUNSKAIA, ELENA; HIRATA, MARIO HIROYUKI; ALVAREZ, JOSE MARIA; D'IMPERIO-LIMA, MARIA REGINA. P2X7 receptor in Bone Marrow-Derived cells aggravates Tuberculosis caused by hypervirulent Mycobacterium bovis. FRONTIERS IN IMMUNOLOGY, v. 8, APR 13 2017. Web of Science Citations: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.