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Role of Inflamassoma in the immunopathogenesis of Placental Malaria

Grant number: 11/19048-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2012
Effective date (End): April 27, 2014
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Cláudio Romero Farias Marinho
Grantee:Aramys Silva dos Reis
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:09/53889-0 - Study of the immunopathological mechanisms involved in pregnancy-associated malaria, AP.JP


Every year at least 50 million pregnant women are exposed to malaria, which represents a high risk of death to the mother and the developing fetus. The placental malaria (PM) is characterized by a sequestration of parasites in the placenta and an excessive and/or prolonged inflammatory response, causing maternal anemia, intrauterine growth retardation and decreased fetal viability. The molecular basis of this placental dysfunction still remain poorly understood, due to the large number of factors potentially involved in PM, combined with difficulties of studying this disease in humans. Important pro-inflammatory factors associated with the disease, such as IL-18 and IL-1b, must be activated via inflamassoma, a multi-protein complex, formed by NLRs like NALP3 and IPAF, ASC and Caspase-1, so they can be secreted to exert its functions. In our hypothesis the inflamassoma can be an important mediator in the pathogenesis of PM and is directly involved in the intense placental inflammation. Thus, this project aims to study the role of NLRs, NALP3 and IPAF, the adapter molecule ASC and Caspase-1 in the pathogenesis of PM, using a murine model of infection. Understanding the aspects of the innate immune response, will bring an important contribution to the knowledge of gestational malaria and contributes to new directions in the search and development of new methodologies for the treatment of PM.

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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)
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)
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)
BARBOZA, RENATO; HASENKAMP, LUTERO; BARATEIRO, ANDRE; MURILLO, OSCAR; MACHADO PEIXOTO, ERIKA PAULA; LIMA, FLAVIA AFONSO; REIS, ARAMYS SILVA; GONCALVES, LIGIA ANTUNES; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F.. Fetal-Derived MyD88 Signaling Contributes to Poor Pregnancy Outcomes During Gestational Malaria. FRONTIERS IN MICROBIOLOGY, v. 10, . (11/17880-8, 15/10892-1, 09/53256-7, 12/14715-9, 16/07030-0, 15/06106-0, 17/03939-7, 11/19048-8, 13/16417-8, 09/53889-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
REIS, Aramys Silva dos. Role of the inflammasome in the immunopathogenesis of severe malaria.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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