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 Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Dario Simões Zamboni
• Grantee: Danilo Sasso Augusto
• Host 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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AUGUSTO, Danilo Sasso. The role of amastins in inflammasome activation and stability of vacuoles infected by Leishmania braziliensis. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.