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

• Grant number: 13/25498-1
• Support type: 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 researcher: Gisele Fabrino Machado
• Grantee: Fernanda Grecco Grano
• Home 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

Abstract

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.

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 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, APR 15 2018. Web of Science Citations: 3.

Academic Publications

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

GRANO, Fernanda Grecco. Investigação do perfil de expressão gênica de receptores tipo toll e citocinas inflamatórias no encéfalo e no baço de cães com leishmaniose visceral. 2017. 76 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina Veterinária..