Leishmania infection and neuroinflammation: Specific chemokine profile and absence of parasites in the brain of naturally-infected dogs.

Visceral leishmaniasis is a chronic disease caused by Leishmania infantum. We aimed to detect the parasite in the brain of fifteen naturally-infected dogs using in situ hybridization and immunohistochemistry, and the gene expression of selected chemokines by RT-qPCR. We detected no parasite in the brain, but perivascular deposition of parasite DNA and IgG in the choroid plexus. We noticed up-regulation of CCL-3, CCL-4 and CCL-5, coherent with T lymphocyte accumulation, stating the brain as a pro-inflammatory environment. Indeed, not necessarily the parasite itself, but rather its DNA seems to act as a trigger to promote brain inflammation during visceral leishmaniasis.

Pro-inflammatory cytokines predominate in the brains of dogs with visceral leishmaniasis: a natural model of neuroinflammation during systemic parasitic infection.

Visceral leishmaniasis is a multisystemic zoonotic disease that can manifest with several symptoms, including neurological disorders. To investigate the pathogenesis of brain alterations occurring during visceral leishmaniasis infection, the expression of the cytokines IL-1ß, IL-6, IL-10, IL-12p40, IFN-γ, TGF-ß and TNF-α and their correlations with peripheral parasite load were evaluated in the brains of dogs naturally infected with Leishmania infantum. IL-1ß, IFN-γ and TNF-α were noticeably up-regulated, and IL-10, TGF-ß and IL-12p40 were down-regulated in the brains of infected dogs. Expression levels did not correlate with parasite load suggestive that the brain alterations are due to the host's immune response regardless of the phase of the disease. These data indicate the presence of a pro-inflammatory status in the nervous milieu of dogs with visceral leishmaniasis especially because IL-1ß and TNF-α are considered key factors for the initiation, maintenance and persistence of inflammation.