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

•We have detected inflammatory infiltrate in the brain of dogs with VL.•Leishmania DNA was detected in the brain and spleen of infected dogs.•Dogs with VL presented up-regulation of TLR-5 and TLR-9 in the spleen.•A small population of infected dogs presented up-regulation of TLR-4 in the brain. Visc...

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Published in:	Veterinary parasitology Vol. 253; pp. 30 - 38
Main Authors:	Grano, Fernanda G., dos S. Silva, José Eduardo, Melo, Guilherme D., de Souza, Milena S., Lima, Valéria M.F., Machado, Gisele F.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-04-2018
Subjects:	Animals Brain - parasitology Brain - pathology Central nervous system Cytokines - genetics Dog Diseases - parasitology Dog Diseases - pathology Dogs Female Gene expression Leishmania infantum Leishmania infantum - physiology Leishmaniasis, Visceral - parasitology Leishmaniasis, Visceral - pathology Leishmaniasis, Visceral - veterinary Life Sciences Male Microbiology and Parasitology Neuroinflammation q-PCR Spleen - parasitology Spleen - pathology Toll-Like Receptors - genetics Neuroinflammation Leishmania infantum Gene expression q-PCR Central nervous system
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Summary:	•We have detected inflammatory infiltrate in the brain of dogs with VL.•Leishmania DNA was detected in the brain and spleen of infected dogs.•Dogs with VL presented up-regulation of TLR-5 and TLR-9 in the spleen.•A small population of infected dogs presented up-regulation of TLR-4 in the brain. 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-α, IFN-γ, IL-1β 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4017 1873-2550 0304-4017
DOI:	10.1016/j.vetpar.2018.02.030