Mechanism of action of lipoxin in the protection against experimental cerebral malaria

• Grant number: 16/12855-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): October 01, 2016
• Effective date (End): September 22, 2020
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: João Luiz da Silva Filho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 19/01578-2 - Host-parasite interactions in the bone marrow: a key role in Malaria pathogenesis, BE.EP.PD

Abstract

Malaria is the most widespread parasitic disease, and despite the many efforts made to eradicate malaria, it accounts for more than half million deaths per year because the host-parasite interactions are not completely understood yet. Cerebral malaria (CM) is a severe neurological complication of infection with Plasmodium falciparum. Even after the appropriate antimalarial treatment, fatality rates range from 10 to 20% which highlights the importance of understanding the pathogenesis of this disease and of implementing new, rapidly acting interventions in combination with anti-plasmodium treatment. Although, cerebral malaria pathogenesis is complex and incompletely understood, observations from animal models and P. falciparum-infected humans support a hypothesis that it involves sequestration of parasitized erythrocytes and leukocytes by the brain microvasculature, and production of pro-inflammatory cytokines, such as IFN-³, TNF-, lymphotoxin-± e IL-12. However, the use of single knockout mutants for several pro-inflammatory cytokines have failed to show an obvious influence on cerebral malaria pathogenesis, suggesting that redundancy among those mediators. Previous results demonstrate that lipoxins, a class of anti-inflammatory lipid mediator derived from lipoxygenase-mediated metabolism of arachidonic acid, limit host damage during experimental cerebral malaria (ECM). In addition, animals treated with lipoxin showed prolonged survival and diminished brain inflammation. Thus, in the search for efficient therapies against CM and a better undertanding of the disease pathogenesis, the aim of this project is to elucidate the mechanisms involved in the lipoxin-induced CM protection and to determine its potential use, as adjuvant therapy, in association with antimalarials to treat severe malaria. (AU)

Scientific publications

(8)

(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)

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, AUG 2018. (12/16525-2, 16/12855-9, 14/20451-0, 16/07030-0)

PADUA, TATIANA A.; TORRES, NATALIA D.; CANDEA, ANDRE L. P.; SOUZA COSTA, MARIA FERNANDA; SILVA, JOHNATAS D.; SILVA-FILHO, JOAO LUIZ; COSTA, FABIO T. M.; ROCCO, PATRICIA R. M.; SOUZA, MARIANA C.; HENRIQUES, MARIA G.. Therapeutic effect of Lipoxin A(4)in malaria-induced acute lung injury. Journal of Leukocyte Biology, v. 103, n. 4, p. 657-670, APR 2018. (16/12855-9)

DOS-SANTOS, JOAO CONRADO KHOURI; SILVA-FILHO, JOAO LUIZ; JUDICE, CARLA C.; KAYANO, ANA CAROLINA ANDRADE VITOR; ALIBERTI, JULIO; KHOURI, RICARDO; DE LIMA, DIOGENES S.; NAKAYA, HELDER; LACERDA, MARCUS VINICIUS GUIMARAES; DE PAULA, ERICH VINICIUS; et al. Platelet disturbances correlate with endothelial cell activation in uncomplicatedPlasmodium vivaxmalaria. PLoS Neglected Tropical Diseases, v. 14, n. 7, JUL 2020. (16/12855-9, 17/18611-7, 12/16525-2)

BITTENCOURT, NAJARA C.; LEITE, JULIANA A.; SILVA, ANA BEATRIZ I. E.; PIMENTA, TAMIRYS S.; SILVA-FILHO, JOAO LUIZ; CASSIANO, GUSTAVO C.; LOPES, STEFANIE C. P.; DOS-SANTOS, JOAO C. K.; BOURGARD, CATARINA; NAKAYA, HELDER I.; et al. Genetic sequence characterization and naturally acquired immune response to Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2). Malaria Journal, v. 17, OCT 31 2018. (13/20509-5, 15/02808-0, 15/20774-6, 12/16525-2, 13/25807-4, 16/12855-9)

SILVA-FILHO, JOAO L.; DOS-SANTOS, JOAO C. K.; JUDICE, CARLA; BERALDI, DARIO; VENUGOPAL, KANNAN; LIMA, DIOGENES; NAKAYA, I, HELDER; DE PAULA, V, ERICH; LOPES, STEFANIE C. P.; LACERDA, MARCUS V. G.; et al. Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients. eLIFE, v. 10, SEP 29 2021. (16/12855-9, 19/01578-2, 17/18611-7)

SILVA-FILHO, JOAO LUIZ; LACERDA, MARCUS V. G.; RECKER, MARIO; WASSMER, SAMUEL C.; MARTI, MATTHIAS; COSTA, FABIO T. M.. Plasmodium vivax in Hematopoietic Niches: Hidden and Dangerous. Trends in Parasitology, v. 36, n. 5, p. 447-458, MAY 2020. (19/01578-2, 16/12855-9, 17/18611-7)

BITTENCOURT, NAJARA CARNEIRO; IUNG ENEMBRECK DA SILVA, ANA BEATRIZ; VIRGILI, NATALIA SILVEIRA; SCHAPPO, ANA PAULA; GERVASIO, JOAO HENRIQUE D. B.; PIMENTA, TAMIRYS S.; KUJBIDA JUNIOR, MARIO A.; VENTURA, ANA MARIA R. S.; LIBONATI, ROSANA M. F.; SILVA-FILHO, JOAO LUIZ; et al. Plasmodium vivaxAMA1: Implications of distinct haplotypes for immune response. PLoS Neglected Tropical Diseases, v. 14, n. 7, JUL 2020. (16/12855-9, 15/02808-0, 12/16525-2)

SILVA-FILHO, JOAO LUIZ; DE OLIVEIRA, LILIAN G.; MONTEIRO, LETICIA; PARISE, PIERINA L.; ZANLUQUI, NAGELA G.; POLONIO, CAROLINA M.; DE FREITAS, CARLA L.; TOLEDO-TEIXEIRA, DANIEL A.; DE SOUZA, WILLIAM M.; BITTENCOURT, NAJARA; et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, OCT 2021. (17/26908-0, 16/00194-8, 20/02159-0, 16/21259-0, 18/13866-0, 16/12855-9, 17/22062-9, 17/26170-0, 17/11828-0, 17/02402-0, 20/02448-2, 18/13645-3, 16/07371-2)