Physical, Chemical, and Immunological Characterization of Extracellular Vesicles from Leishmania (V.) lainsoni and Leishmania (V.) naiffi

• Grant number: 24/05861-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luiz Felipe Domingues Passero
• Grantee: Italo Novais Cavallone
• Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil

Abstract

Leishmaniasis is a disease caused by parasites of the genus Leishmania, which produce structures known as extracellular vesicles (EVs) that carry a set of molecules associated with communication between parasite-parasite and parasite-host. These vesicles can suppress or stimulate the immune response of the vertebrate host. In this context, the present study aims to investigate the morphological characteristics, proteome, and immunomodulatory potential of the EVs from L. (V.) lainsoni and L. (V.) naiffi, neglected Amazonian species that have received little scientific attention, although reports suggest increasing incidence, urbanization, and resistance to treatment. The EVs will be purified through ultracentrifugation, and the morphological characterization will be analyzed using nanoparticle tracking and scanning electron microscopy, as well as freeze-fracture to observe topology. The protein content will be characterized by mass spectrometry. For the immunological analyses, both in vitro and in vivo experiments will be conducted. In vitro, murine macrophages will be stimulated with the EVs to assess the stimulatory or suppressive potential of the EVs on innate immunity. In vivo experiments will evaluate the impact of EVs on cellular immune response through cytokine measurement and T lymphocyte frequency, as well as the humoral immune response by quantifying total IgG, IgG1, IgG2a, and IgG2b against EVs. The same set of antibodies will be measured in serum from patients with leishmaniasis to determine whether the EVs play a significant role in modulating immunity during natural human infection. It is expected that the data obtained from this project will describe and detail the importance of understanding neglected Leishmania species, as well as explore the immunomodulatory potential of these structures.