In vitro study model for evaluating the response of glial cells to Leishmania infantum

• Grant number: 25/12390-5
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: April 30, 2028
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Gisele Fabrino Machado
• Grantee: Gisele Fabrino Machado
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• City of the host institution: Araçatuba
• Associated researchers: Flavia Lombardi Lopes ; Guilherme Dias de Melo ; Valéria Marçal Felix de Lima
• Associated scholarship(s): 25/24755-8 - In vitro study for evaluating the response of glial cells to Leishmania infantum, BP.DR

Abstract

Visceral leishmaniasis (VL) is a neglected tropical zoonosis that is distributed globally and whose main urban reservoir is the domestic dog. Leishmania causes chronic and progressive disease, which may be asymptomatic or manifest a wide range of nonspecific symptoms. In recent years, studies have shown that leishmaniasis can affect the central (CNS) and peripheral (PNS) nervous systems, in addition to the parasite's ability to cross the blood-brain barrier (BBB) ¿¿and blood-cerebrospinal fluid (BHL), disseminating into the cerebrospinal fluid (CSF) and resulting in possible neurological manifestations. Chronic peripheral inflammation can trigger neuroinflammation, with the activation of microglia and astrocytes, resulting in histopathological changes frequently observed in infected animals and in the pro-inflammatory gene expression profile in nervous tissue. A deeper understanding of the mechanisms involved in cerebral leishmaniasis can be benefited by in vitro experimental models, which allow studying the interaction between Leishmania, glial cells and inflammatory cytokines in a standardized manner and without interference and individual variations observed in patients. Thus, our proposal in this project is to evaluate the response of astrocytes and microglia to different stimuli originating from Leishmania infantum (whole parasite, soluble antigens, and conditioned astrocyte and microglia culture medium). Our control, stimulation of cells with IFN-¿, also aims to mimic the possible peripheral stimulation of glial cells that can occur in patients with visceral leishmaniasis. Total mRNA sequencing will be performed to characterize and interpret the functioning of the genome of these cells and to better understand the development of the changes that occur in the nervous tissue of infected patients. The response of the stimulated cells will be evaluated by measuring the proteins in the cell lysate and cytokines in the culture supernatant. (AU)