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Investigation of Toll-like receptors activation in the brain of dogs with visceral leishmaniasis

Grant number: 13/25498-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Gisele Fabrino Machado
Grantee:Fernanda Grecco Grano
Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated scholarship(s):15/10591-1 - Dynamic brain imaging during experimental visceral leishmaniasis: investigation of microglial response and Leishmania donovani brain tropism, BE.EP.DR


Visceral leishmaniasis (VL) is a disease that can present with several clinical manifestations in dogs, raging from subclinical to generalized disorders. Chronically infected dogs may present neurological involvement; however there are few reports characterizing the lesions observed and elucidating the pathogenesis of the neurological form of the VL. There are evidences of inflammation in the brain of these dogs by the observation of infiltration of T lymphocytes, activation of glial cells, degenerative changes of neurons, presence of enzymes of the group of matrix metalloproteinases, as well as meningitis and choroiditis. In sequence to previous projects, where the aims were to evaluate the inflammatory lesions of the brain in dogs with VL and investigate the mechanisms related to its occurrence, we propose to evaluate and determine the profile of Toll-like receptors (TLRs) in the central nervous system (CNS) (brain) and to compare with the periphery (spleen) in naturally infected dogs by Leishmania infantum. Moreover, we aim to investigate the activation of TLRs signaling pathways by the evaluation of MyD88, TRIF and NF-kB, as well as the production of pro-inflammatory cytokines: IL-1², IL-2, IL-4, IL-6, IL-17, TNF-± and IFN-³. Histopathological analysis and characterization of the brain lesions also will be performed and, posteriorly, these inflammatory lesions will be correlated with the TLRs and cytokines profiles.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GRANO, FERNANDA GRECCO; DOS SANTOS SILVA, JOSE EDUARDO; DE MELO, GUILHERME DIAS; MACHADO, GISELE FABRINO. Leishmania hide-and-seek: Parasite amastigotes in the choroid plexus of a dog with neurological signs in an endemic municipality in Brazil. VETERINARY PARASITOLOGY- REGIONAL STUDIES AND REPORTS, v. 17, p. 4-pg., . (16/02384-9, 14/01202-9, 13/25498-1)
GRANO, FERNANDA G.; SILVA, JOSE EDUARDO DOS S.; MELO, GUILHERME D.; DE SOUZA, MILENA S.; LIMA, VALERIA M. F.; MACHADO, GISELE F.. Toll-like receptors and cytokines in the brain and in spleen of dogs with visceral leishmaniosis. Veterinary Parasitology, v. 253, p. 30-38, . (13/25498-1, 16/02384-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
GRANO, Fernanda Grecco. Investigation of the gene expression profile of toll-like receptors and inflammatory cytokines in the brain and in the spleen of dogs with visceral leishmaniasis. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária. Araçatuba Araçatuba.

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