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

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.