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Global expression analysis of macrophages infected with Leishmania chagasi

Grant number: 12/18347-4
Support type:Regular Research Grants
Duration: December 01, 2012 - May 31, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Paulo Eduardo Martins Ribolla
Grantee:Paulo Eduardo Martins Ribolla
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Diego Peres Alonso ; Hiro Goto

Abstract

In Brazil, visceral leishmaniasis (VL) is caused by the protozoan Leishmania infantum chagasi, obligate intracellular parasite of macrophages, and transmitted by the sandfly Lutzomyia longipalpis, the main reservoirs of zoonotic cycle involved are domestic dogs and wild canids.Interestingly, lipid disorders have been reported in human patients and even domestic dogs with active LV. The lipid profile in most cases is characterized by high levels of triglycerides (TG) and very low density lipoproteins (VLDL), on the other hand, are reported low levels of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoproteins (HDL). A likely explanation for these findings is the greater dependence of lipids and proteins as an energy source of the amastigote forms of the parasite within the infected macrophages and the presence of cholesterol is important for macrophage infection by the parasite.Since the influence of serum lipid levels on infection by L. infantum chagasi has been demonstrated by several studies independently, a comprehensive study of the gene expression profile of the infected host cell, as well as their parasite in the presence of different lipid fractions (VLDL, LDL and HDL), can represent an important advance in identifying key genes in this complex host-parasite interactions. In this context, drugs that modulate lipid levels can be used as adjuvants in the treatment of VL. An interesting approach is the evaluation of fibrates, that are hypolipidemic drugs used to reduce levels of triglycerides and cholesterol, as a candidate to control LVA.Armed with this information, this project aims to carry out a global analysis of gene expression profiling, RNA-Seq, in cultured human macrophages infected with L. infantum chagasi in the presence of different lipoprotein fractions. In addition, a secondary goal is an in vitro study of macrophage-parasite interaction in human macrophages incubated with promastigotes of L. infantum chagasi in the presence of synthetic agonists of PPAR±, in order to evaluate the effects of these agonists in the parasite load of infected macrophages. (AU)