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Impact of autophagy and inflammasome on the pathogenesis of Placental Malaria

Grant number: 17/03939-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2017
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Cláudio Romero Farias Marinho
Grantee:André Filipe Rivais Martins Barateiro
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Malaria is a severe public health problem around the world, especially in developing countries where it is responsible for approximately 500 000 deaths every year. Pregnant women are more prone to develop severe infection than non-pregnant counterparts due to the existence are of the placenta. Erythrocytes infected with Plasmodium spp. accumulate inside this organ leading to the development of a severe immunopathology known as Malaria in Pregnancy (MiP). The disease is characterized by a severe inflammatory state that has deleterious consequences to the mother and the foetus, leading to high maternal and fetal mortality, abortion, intrauterine growth restriction, foetal growth restriction and preterm delivery. Recently, significant advances were done regarding the understanding of this disease; yet, there are several factors which contribution to MiP pathogenesis remains unknown. Placental homeostasis must be meticulously controlled to ensure the development of the growing foetus. As such, there are molecular mechanisms that contribute to cellular homeostasis such as autophagy, a programme of "cell recycling" which is activated under certain stress conditions. Besides inflammation, this mechanism can be trigger by inflammasome, a molecular complex associated to the production of proinflammatory cytokines such as IL-1² and IL-18, abundantly produced during MiP. Therefore, we hypothesized that local inflammation can alter the autophagy profile in the placenta. Consequently, this will modulate inflammasome activity contributing to MiP pathology. Our work will allow us to better understand how certain unknown aspects of immune response contribute to this immunopathology hopefully leading to the development of new therapeutical strategies. (AU)

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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)
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)
PANDYA, YASH; MARTA, ALEXANDER; BARATEIRO, ANDRE; BANDEIRA, CARLA LETICIA; DOMBROWSKI, JAMILLE GREGORIO; COSTA, JOAO; FARIAS MARINHO, CLAUDIO ROMERO; PENHA-GONCALVES, CARLOS. TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria. Infection and Immunity, v. 89, n. 8, . (19/12068-5, 16/07030-0, 12/04755-3, 14/09964-5, 17/03939-7, 20/06747-4)
BARATEIRO, ANDRE; PEREIRA, MARCELO L. M.; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F.. Contribution of Murine Models to the Study of Malaria During Pregnancy. FRONTIERS IN MICROBIOLOGY, v. 10, . (12/10081-5, 17/05782-8, 17/03939-7, 18/20468-0)
DOMBROWSKI, JAMILLE GREGORIO; BARATEIRO, ANDRE; MACHADO PEIXOTO, ERIKA PAULA; CLAUDIO DA SILVA BARROS, ANDRE BOLER; DE SOUZA, RODRIGO MEDEIROS; CLARK, TAANE GREGORY; CAMPINO, SUSANA; WRENGER, CARSTEN; WUNDERLICH, GERHARD; PALMISANO, GIUSEPPE; et al. Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon. PLoS Neglected Tropical Diseases, v. 15, n. 4, . (17/03966-4, 17/03939-7, 18/18257-1, 19/12068-5, 15/26722-8, 17/24267-7, 20/06747-4, 18/20468-0, 20/04923-0, 18/15549-1, 17/05782-8)
KASSA, MESERET W.; HASANG, WINA; BARATEIRO, ANDRE; DAMELANG, TIMON; BREWSTER, JESSICA; DOMBROWSKI, JAMILLE G. G.; LONGLEY, RHEA J. J.; CHUNG, AMY W.; WUNDERLICH, GERHARD; MUELLER, IVO; et al. Acquisition of antibodies to Plasmodium falciparum and Plasmodium vivax antigens in pregnant women living in a low malaria transmission area of Brazil. Malaria Journal, v. 21, n. 1, p. 14-pg., . (19/12068-5, 18/20468-0, 17/50181-2, 17/03939-7)
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)
LIMA, FLAVIA AFONSO; BARATEIRO, ANDRE; DOMBROWSKI, JAMILLE GREGORIO; DE SOUZA, RODRIGO MEDEIROS; COSTA, DOUGLAS DE SOUSA; MURILLO, OSCAR; EPIPHANIO, SABRINA; GONCALVES, LIGIA ANTUNES; FARIAS MARINHO, CLAUDIO ROMERO. Plasmodium falciparum infection dysregulates placental autophagy. PLoS One, v. 14, n. 12, . (17/03939-7, 17/05782-8, 13/16417-8, 12/04755-3, 16/07030-0, 15/06106-0, 13/00981-1, 18/20468-0)
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)

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