Advanced search
Start date
Betweenand

Investigation of the role of amastins in the inflammasome activation and in the translocation of Leishmania molecules into the macrophage cytoplasm

Grant number: 17/04243-6
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2017
Effective date (End): January 31, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Dario Simões Zamboni
Grantee:Danilo Sasso Augusto
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion, AP.TEM

Abstract

Leishmaniasis is a neglected tropical disease that affects around 12 million people worldwide. Its symptoms range from a self-healing skin lesion to death. The leishmaniasis etiological agents are parasites from the Leishmania genus. The Leishmania spp. life cycle occurs either on the digestive system from insects of the phlebotominae subfamily or within the parasitophore vacuole from mammal phagocytic cells, mainly macrophages. The NLRP3 inflammasome is a cytoplasmic complex with high molecular weight, which senses patterns related to membrane damage. Recently, the contribution of NLRP3 to the IL-1² and nitric oxide production, during the inflammatory response against Leishmania spp. was described as important for inflammatory and microbicidal effects. During the infection, the parasite survival and replication rely on its capacity to modulate and subvert the macrophage microbicidal and inflammatory responses. Various virulence factors were described in Leishmanis spp. including lipophosphoglycans and the metalloprotease GP63. However, how the parasites translocate their virulence factors to the macrophage cytoplasm is unknown. Recently, a family of parasite membrane glycoproteins was silenced by RNAi, allowing to comprehend the role of these family in the membrane interaction that occurs between the parasite and the parasitophorous vacuole membranes. This work aims to comprehend how NLRP3 responds to a Leishmania braziliensis with silenced expression of amastins. In addition, we will investigate whether amastins are related with the translocation of virulence factors from Leishmania spp. to macrophage cytoplasm. Our hypothesis (initially corroborated by preliminary results) is that amastins are related in the NLRP3 activation during infection by L. braziliensis. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)