Neuropathogenesis of canine visceral leishmaniasis: investigation of inflammatory mediators

Abstract

Visceral leishmaniasis (VL) is an anthropozoonosis with worldwide distribution, and in Brazil it is caused by the protozoan Leishmania chagasi. The disease affects mainly the organs with mononuclear phagocyte system cells, such as spleen, lymph nodes, bone marrow, liver, besides skin. As occurs in other protozoan diseases, the peripherical infection by L. chagasi also promotes central nervous system (CNS) alterations, and in dogs with VL there are reports of meningitis, choroiditis, anti-Leishmania antibodies in the cerebrospinal fluid, and massive inflammatory cells infiltration in the brain. Following on previous research projects and on our aims to evaluate the brain lesions in dogs with VL and to investigate the mechanisms by which it occurs, we propose to evaluate the occurrence of inflammatory mediators within the CNS (brain and cerebrospinal fluid) and in the periphery (spleen, serum and PBMC) of dogs naturally infected by L. chagasi, including the enzymes COX-2, 5-LOX and iNOS, the eicosanoids PGE2 and LTB4, nitric oxide, lipid bodies in leukocytes, the gene expression of the chemokines MCP-1, MCP-2, MIP-1alpha, MIP-1beta, RANTES, CXCL-10 and CX3CL1, the presence of albumin and IgG as well as of the IgG receptors Fc-gammaRI and Fc-gammaRIII. The occurrence of the protozoan within the CNS will also be investigated.