Toll-like receptors and cytokines in the brain and in spleen of dogs with visceral leishmaniosis

Author(s)

Grano, Fernanda G. ^[1] ; Silva, Jose Eduardo dos S. ^[1] ; Melo, Guilherme D. ^[2] ; de Souza, Milena S. ^[1] ; Lima, Valeria M. F. ^[1] ; Machado, Gisele F. ^[1]

Affiliation

^[1] Univ Estadual Paulista, UNESP, Fac Med Vet Aracatuba, Rua Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

^[2] Inst Pasteur, Dept Infect & Epidemiol, Lab Proc Infect Trypanosomatides, 25-28 Rue Dr Roux, F-75724 Paris 15 - France

• Document type: Journal article
• Source: Veterinary Parasitology; v. 253, p. 30-38, APR 15 2018.
• Web of Science Citations: 3

Abstract

Visceral leishmaniosis (VL) is a multisystem disease that affects domestic dogs and can have several clinical manifestations, including some rare reports of neurological clinical signs, or it may remain asymptomatic, depending on the individual immune response against the Leishmania parasite. VL involves immune system sensors, such as the Toll-like receptors (TLRs), that are related to innate immunity and inflammation. Previously, we have reported the presence of brain inflammation in infected dogs. Here, we investigated the gene expression profile of TLRs 1-10 in the brain and the spleen of infected dogs, along with the production of proinflammatory cytokines (TNF-alpha, IFN-gamma, IL-1 beta and IL-6) with the aim of explaining the origin of brain inflammation. The gene expression of TLRs has varied according to the tissue evaluated. In the brain, TLR-4 was only up-regulated in a small subpopulation of infected dogs, while in the spleen, we detected an increase in TLR-5 and TLR-9 transcripts, as well as a reduction in TLRs 2-4 and TLR-10. All cytokines except IL-6 were detected in infected dogs. Moreover, we detected Leishmania DNA in all infected dogs in both tissues evaluated. In the histopathological analysis, we observed a predominance of lymphoplasmacytic infiltrate, mainly in leptomeninges and choroid plexuses, ranging from mild to intense. This study provides the first insight into the TLRs profile in the brain and the spleen during canine VL and provides support to confirm the involvement of sensors of the innate immune system sensors against L. infantum parasites. (AU)

• FAPESP's process: 16/02384-9 - BRAIN INFLAMMATION IN DOGS WITH VISCERAL LEISHMANIASIS: Activation of Innate and Adaptative Immune Response.
• Grantee: Gisele Fabrino Machado
• Support type: Regular Research Grants
• FAPESP's process: 13/25498-1 - Investigation of Toll-like receptors activation in the brain of dogs with visceral leishmaniasis
• Grantee: Fernanda Grecco Grano
• Support type: Scholarships in Brazil - Doctorate