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The role of endothelial cells in the immunopathogenesis of murine malaria-associated ALI/ARDS: effects and mechanisms

Grant number: 14/20451-0
Support Opportunities:Regular Research Grants
Duration: February 01, 2015 - January 31, 2017
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Sabrina Epiphanio
Grantee:Sabrina Epiphanio
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Cláudio Romero Farias Marinho


Malaria is a major global health problem, especially in tropical and subtropical regions. In Brazil, 99% of the cases are concentrated in the Legal Amazon, where Plasmodium vivax are the major causes of disease and can be fatal. Plasmodium ssp. can lead to serious pulmonary condition complications with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Respiratory complications are characterized by decreased capacity for gas exchange, increased leukocyte activity and inflammatory mediators in the lungs. A large number of potentially involved factors associated with significant difficulties in the study of disease in humans causes the molecular basis of lung dysfunction remains poorly understood, leading to high mortality in health facilities. Mechanisms related to innate immunity have been shown to be essential for the early control of Plasmodium infection through increased cytokines and activation of the cellular immune response. However, excessive and / or prolonged inflammatory response contributes to the pathogenesis and symptoms associated with severe malaria. Receptors Toll-like molecular patterns play a critical role in detecting pathogens and activation of innate immune response. Other important aspect that may be associated with the development of severe malaria is the ability of parasitized erythrocytes to be sequestered in the microvasculature of the tissue, activation of lung endothelial cells and increased pulmonary vascular permeability. This project aims to understand the role of some components of innate immunity in ALI/ARDS and the effect of adhesion of infected erythrocytes to endothelial cells, a study that will be addressed in a murine model of infection. Knowledge of aspects of the innate immune response will bring a significant contribution to the understanding of malaria associated ALI/ARDS, and enable studies aimed at developing new methodologies for the treatment of disease. (AU)

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Scientific publications (10)
(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)
REIS, ARAMYS S.; BARBOZA, RENATO; MURILLO, OSCAR; BARATEIRO, ANDRE; PEIXOTO, ERIKA P. M.; LIMA, FLAVIA A.; GOMES, VINICIUS M.; DOMBROWSKI, JAMILLE G.; LEAL, VINICIUS N. C.; ARAUJO, FRANCIELE; et al. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes. SCIENCE ADVANCES, v. 6, n. 10, . (14/09964-5, 15/23395-6, 14/20451-0, 17/03939-7, 11/19048-8, 17/05782-8, 13/16417-8, 16/07030-0, 12/16525-2, 12/04755-3, 15/50650-7, 18/20468-0, 13/00981-1, 11/17880-8, 15/06106-0)
BASTOS, MARCELE F.; KAYANO, ANA CAROLINA A. V.; SILVA-FILHO, JOAO LUIZ; DOS-SANTOS, JOAO CONRADO K.; JUDICE, CARLA; BLANCO, YARA C.; SHRYOCK, NATHANIEL; SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; FRANCELIN, CAROLINA; et al. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria. FASEB JOURNAL, v. 32, n. 8, p. 4470-4481, . (12/16525-2, 16/12855-9, 14/20451-0, 16/07030-0)
PEREIRA, MARCELO L. M.; ORTOLAN, LUANA S.; SERCUNDES, MICHELLE K.; DEBONE, DANIELA; MURILLO, OSCAR; LIMA, FLAVIA A.; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS. Mediators of Inflammation, . (09/53256-7, 14/09964-5, 12/10081-5, 14/20451-0)
BARBOZA, RENATO; LIMA, FLAVIA AFONSO; REIS, ARAMYS SILVA; MURILLO, OSCAR JAVIER; MACHADO PEIXOTO, ERIKA PAULA; BANDEIRA, CARLA LETICIA; FOTORAN, WESLEY LUZETTI; SARDINHA, LUIS ROBERTO; WUNDERLICH, GERHARD; BEVILACQUA, ESTELA; et al. TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria. SCIENTIFIC REPORTS, v. 7, . (12/16525-2, 11/17880-8, 14/20451-0, 14/09964-5, 15/06106-0, 13/00981-1, 11/19048-8, 13/16417-8, 09/53889-0)
PEREIRA, MARCELO L. M.; ORTOLAN, LUANA S.; SERCUNDES, MICHELLE K.; DEBONE, DANIELA; MURILLO, OSCAR; LIMA, FLAVIA A.; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS. Mediators of Inflammation, v. 2016, p. 12-pg., . (12/10081-5, 09/53256-7, 14/09964-5, 14/20451-0)
DOMBROWSKI, JAMILLE GREGORIO; DE SOUZA, RODRIGO MEDEIROS; MENDES SILVA, NATERCIA REGINA; BARATEIRO, ANDRE; EPIPHANIO, SABRINA; GONCALVES, LIGIA ANTUNES; FARIAS MARINHO, CLAUDIO ROMERO. Malaria during pregnancy and newborn outcome in an unstable transmission area in Brazil: A population-based record linkage study. PLoS One, v. 13, n. 6, . (15/06106-0, 17/03939-7, 12/04755-3, 14/20451-0, 14/09964-5, 09/53889-0)
PEREIRA, MARCELO L. M.; MARINHO, CLAUDIO R. F.; EPIPHANIO, SABRINA. Could Heme Oxygenase-1 Be a New Target for Therapeutic Intervention in Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome?. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, . (12/10081-5, 14/20451-0, 16/07030-0)
DOMBROWSKI, JAMILLE G.; SOUZA, RODRIGO M.; CURRY, JONATHAN; HINTON, LAURA; SILVA, NATERCIA R. M.; GRIGNARD, LYNN; GONCALVES, LIGIA A.; GOMES, ANA RITA; EPIPHANIO, SABRINA; DRAKELEY, CHRIS; et al. G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon. Malaria Journal, v. 16, . (12/04755-3, 14/20451-0, 14/09964-5, 15/06106-0, 16/13465-0)
ORTOLAN, LUANA DOS SANTOS; SERCUNDES, MICHELLE KLEIN; MOURA, GABRIEL CANDIDO; QUIRINO, THATYANE DE CASTRO; DEBONE, DANIELA; COSTA, DOUGLAS DE SOUSA; MURILLO, OSCAR; FARIAS MARINHO, CLAUDIO ROMERO; EPIPHANIO, SABRINA. Endothelial Protein C Receptor Could Contribute to Experimental Malaria-Associated Acute Respiratory Distress Syndrome. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2019, . (14/20451-0, 13/20718-3, 13/00981-1, 17/05782-8, 17/00077-4)
DOMBROWSKI, JAMILLE GREGORIO; DE SOUZA, RODRIGO MEDEIROS; LIMA, FLAVIA AFONSO; BANDEIRA, CARLA LETICIA; MURILLO, OSCAR; COSTA, DOUGLAS DE SOUSA; MACHADO PEIXOTO, ERIKA PAULA; CUNHA, MARIELTON DOS PASSOS; DE ANDRADE ZANOTTO, PAOLO MARINHO; BEVILACQUA, ESTELA; et al. Association of Malaria Infection During Pregnancy With Head Circumference of Newborns in the Brazilian Amazon. JAMA NETWORK OPEN, v. 2, n. 5, . (14/17766-9, 18/20468-0, 12/04755-3, 13/21728-2, 14/20451-0, 14/09964-5, 15/06106-0, 13/00981-1, 16/08204-2, 13/16417-8, 09/53889-0)

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