| Grant number: | 17/03939-7 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | October 01, 2017 |
| End date: | 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 |
Abstract 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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