Effect of lysosomal proteins - LAMP2- on the infection of phagocytic and non-phagocytic cells by Leishmania amazonensis: an analysis by confocal microscopy

• Grant number: 24/01463-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Marina Tiemi Shio
• Grantee: Arianne Emily Fernandes Araujo
• Host Institution: Universidade de Santo Amaro (UNISA). São Paulo , SP, Brazil

Abstract

Leishmaniasis is an endemic disease in several countries, including Brazil. Cutaneous leishmaniasis is the most predominant and is mainly associated with the species Leishmania (L) amazonensis and L. (V) braziliensis. Visceral leishmaniasis can lead to death in 90% of untreated cases and is caused by L. infantum chagasi. The protozoan has two evolutionary forms promastigote and amastigote. Promastigotes are phagocytosed by macrophages, neutrophils and dendritic cells. The process of internalization of parasites occurs mainly via phagocytosis mediated by receptors and recently the involvement of recruitment and exocytosis of lysosomes has been described, a mechanism used to repair the host cell membrane damaged by the parasite's flagellum. After internalization of promastigotes, phagosomes are formed, which fuse with primary lysosomes, forming the parasitophorous vacuole (PV). In this vesicle, the promastigote forms undergo a rapid transformation into amastigotes. VPs contain molecules from the endocytic pathway, including lysosomal membrane-associated proteins (LAMP-1 and LAMP-2). Studies in the literature show the presence of LAMP-1/LAMP-2 as markers of PVs, however, there is still no research that proves the role of these proteins in the process and establishment of infection by the protozoan. The objective of the present project is to evaluate the effect of LAMP-2 on infection by protozoa of the species Leishmania amazonensis of phagocytic and non-phagocytic cells. This project will contribute to a better understanding of the mechanisms and establishment of infection in cells and, thus, contribute to improving the fight against this neglected and widely distributed disease in Brazil.