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The role of cytoadherence and Toll-like receptors (TLRs) in the immunopathogenesis of murine severe malaria associated to acute respiratory distress syndrome

Grant number: 13/20718-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2015
Effective date (End): October 31, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Sabrina Epiphanio
Grantee:Luana dos Santos Ortolan
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Malaria is a global health problem, especially in tropical and subtropical regions. In Brazil, 99% of the cases are concentrated in the Amazon Region where infections by Plasmodium vivax are the major cause of morbidity and which can also be fatal. Plasmodium ssp. infections can lead to severe respiratory conditions including pulmonary complications named as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pulmonary complications are characterized by reduced capacity for gas exchange, increased leukocyte activity and inflammatory mediators in the lungs. The molecular basis of pulmonary dysfunction still remains poorly understood because the large number of factors potentially involved in this disease and the difficulties in the study of this disease in humans, resulting in high mortality in health facilities. Mechanisms related to innate immunity have proved to be important for the early control of Plasmodium infection through increased cytokines and activation of cellular immune response. However, excessive inflammatory response and/ or prolonged contributes to the pathogenesis and symptoms associated with severe malaria. Receptors for molecular patterns - Toll-like play a critical role in the detection of pathogens and activation of innate immune response. Other relevant aspects that may be associated with the development of severe malaria is the ability of parasited erythrocytes to be sequestered in the microvasculature of tissues, activation of pulmonary 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 the innate immune response will bring an important 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 (4)
(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)
SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; JULIO, VIVIANE DA SILVA; BELLA, LEONARDO M.; QUIRINO, THATYANE DE CASTRO; DEBONE, DANIELA; CARNEIRO-RAMOS, MARCELA S.; CHRISTOFFOLETE, MARCELO A.; MARTINS, JOILSON O.; D'IMPERIO LIMA, MARIA REGINA; et al. lockade of caspase cascade overcomes malaria-associated acute respiratory distress syndrome in mic. CELL DEATH & DISEASE, v. 13, n. 2, . (20/03163-1, 13/20718-3, 15/06106-0, 20/06747-4, 20/03175-0)
SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; DEBONE, DANIELA; SOEIRO-PEREIRA, PAULO V.; GOMES, ELIANE; AITKEN, ELIZABETH H.; NETO, ANTONIO CONDINO; RUSSO, MOMTCHILO; D' IMPERIO LIMA, MARIA R.; ALVAREZ, JOSE M.; et al. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice. PLOS PATHOGENS, v. 12, n. 12, . (09/53256-7, 13/20718-3, 11/19525-0, 10/11925-7, 09/53889-0, 10/19439-4)
QUIRINO, THATYANE DE CASTRO; ORTOLAN, LUANA DOS SANTOS; SERCUNDES, MICHELLE KLEIN; FARIAS MARINHO, CLAUDIO ROMERO; TURATO, WALTER MIGUEL; EPIPHANIO, SABRINA. Lung aeration in experimental malaria-associated acute respiratory distress syndrome by SPECT/CT analysis. PLoS One, v. 15, n. 5, . (13/20718-3, 17/05782-8)
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)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ORTOLAN, Luana dos Santos. Cytoadhesion in the immunopathogenesis of malaria-associated acute respiratory distress syndrome.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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