Characterization of autophagic activity and inflammasome in placental malaria

• Grant number: 16/07030-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2017
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Cláudio Romero Farias Marinho
• Grantee: Cláudio Romero Farias Marinho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Rodrigo Medeiros Martorano ; Sabrina Epiphanio
• Associated research grant(s): 17/50181-2 - A novel approach to identify the specific antibody characteristics important for protection from malaria in pregnant women, AP.R SPRINT

Abstract

Malaria in pregnancy is a major public health problem in countries where the disease is endemic, causing maternal and infant morbidity and mortality. It remains unclear why pregnant women are more susceptible to malaria. However, it is known that the placenta provides a favorable environment to the development of certain parasite subpopulations, triggering an intense inflammatory infiltrate that is associated with abortions, intrauterine growth retardation, premature births and low birth weight. Autophagy is an essential process for cell survival during stress, such as infections or cell exposure to microbial products. It also plays a role in the trophoblast response to stress agents in normal pregnancy, allowing these cells to adapt to a variety of insults usually found in pregnant women. Certain signaling molecules related to the immune system can regulate autophagy. Although in recent years many studies have defined the clinical manifestations of malaria during pregnancy, the cellular and molecular mechanisms associated with the inflammatory process are not yet fully understood. In this project, we intend to characterize the autophagic activity and its possible relationship to the inflammasome in human placentas infected with Plasmodium falciparum and also in a murine experimental model that mimics the human disease. This study will not only make an important contribution to a better understanding of placental malaria, but could also enable new studies directed to the development of new diagnostic methods and gestational malaria treatment. (AU)

Scientific publications

(7)

(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)

CAMPOS, MONICA C.; DOMBROWSKI, JAMILLE G.; PHELAN, JODY; MARINHO, CLAUDIO R. F.; HIBBERD, MARTIN; CLARK, TAANE G.; CAMPINO, SUSANA. Zika might not be acting alone: Using an ecological study approach to investigate potential co-acting risk factors for an unusual pattern of microcephaly in Brazil. PLoS One, v. 13, n. 8, AUG 15 2018. (12/04755-3, 16/07030-0)

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, MAR 2020. (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, AUG 2021. (19/12068-5, 16/07030-0, 12/04755-3, 14/09964-5, 17/03939-7, 20/06747-4)

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, DEC 5 2019. (17/03939-7, 17/05782-8, 13/16417-8, 12/04755-3, 16/07030-0, 15/06106-0, 13/00981-1, 18/20468-0)

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, MAY 16 2018. (12/10081-5, 14/20451-0, 16/07030-0)

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, JAN 29 2019. (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)