Lipidome of Leishmania (Leishmania) infantum-infected THP-1 macrophages and amastigotes and their relationship with the transcriptome and metabolome.

Abstract

Leishmaniases are neglected diseases caused by parasites of the genus Leishmania, prevalent in countries situated in tropical and subtropical areas. The most serious form is visceral leishmaniasis (VL), caused by Leishmania (Leishmania) infantum, which is lethal if untreated. Besides the classic systemic manifestations of VL, changes in the lipid profile are observed both in infected humans and animals, characterized by an increase in triglycerides (TG), very-low density lipoproteins (VLDL), and a decrease in high-density lipoproteins (HDL). Our previous study has shown that upon infection by L. infantum THP-1 cells exhibit changes in the expression of genes related to lipid metabolism, suggesting a possible accumulation of intracellular cholesterol. Furthermore, data from the literature and from the research group of Professor Hiro Goto indicated that lipids play an important role in the establishment and progression of VL. Therefore, characterizing the changes in the lipid composition of infected THP-1 cells and of parasites may contribute to understanding how lipids participate in the Leishmania-macrophage interaction, providing insights into the progression of the infection. In parallel, we have transcriptomic data and ongoing metabolomic analysis with L. infantum-infected THP-1 cells. Thus, the aim of this work is to characterize the lipid profile of both L. infantum-infected THP-1 cells and the parasite L. infantum through lipidomic analysis, correlating them with changes in the expression of genes and metabolites interaction for a better understanding of infection progression and identification of biomarkers of progression. (AU)