Neuropathogenesis of experimental visceral leishmaniasis: investigation of parasite migration and immune response in a murine model

Abstract

Visceral leishmaniasis (VL) is a multisystemic anthropozoonotic disease that can manifest with several symptoms, including neurological disorders. There are published papers concerning brain inflammatory alterations in dogs naturally infected with Leishmania infantum, but the actual parasite migration towards the nervous milieu remains to be proven. Several authors have established animal models to study the pathogenesis of VL, but focusing solely on the organs of the mononuclear phagocyte system, such as spleen and liver. The establishment of a laboratory model to study the neuropathogenesis of VL, together with a state-of-the-art procedure to generate bioluminescent parasites and to evaluate their localization in vivo in infected animals will be helpful to provide evidences of Leishmania entrance into the central nervous system. Using bioluminescent assays, RT-qPCR and immunohistology we aim to determine the parasite migration towards the brain, taking into account the time of infection and the pathways by which this occurs in a murine model. Further, using RT-qPCR and ELISA, we will determine the brain immunosignalling, the peripheral pro/anti-inflammatory response, as well as the antibody response, in order to assess the inflammatory status in the nervous milieu. (AU)