Abstract
Simple SummaryThe immunopathogenesis of leishmaniasis is not completely understood. Exosomes are extracellular vesicles produced by most eukaryotic cells, containing various molecular constituents with biological effects (e.g., proteins, peptides, RNA). They play an important role in cell-to-cell signaling. Recently, exosomal microRNA were demonstrated to be able to regulate gene expression and protein production in mammalian cells, serving as potential biomarkers of disease. The microRNA miR-122 is a biomarker of hepatic damage widely studied in mice in the course of Leishmania infection. Leishmania organisms can interfere with miR-122 production leading to a dysfunction in cholesterol metabolism ensuring its proliferation in the infected host. In this study, we suggest that such a phenomenon may also occur in dogs affected by Leishmania infection.Current knowledge on the role of exosomal microRNA (miRNA) in canine leishmaniasis (CL), with particular regards to the interaction between miR-122 and lipid alterations, is limited. The aim of this study was to isolate/characterize exosomes in canine serum and evaluate the expression of miR-122 in ten healthy and ten leishmaniotic dogs. Serum exosomes were isolated using a polymer-based kit, ExoQuick® and characterized by flow cytometry and transmission electron microscopy, whereas miR-122-5p expression was evaluated by quantitative reverse-transcriptase polymerase chain reaction. A significant decreased expression of exosomal miR-122-5p, decreased serum levels of high-density lipoproteins, and increased serum levels of low-density lipoproteins were seen in leishmaniotic dogs when compared with healthy dogs. These results suggest that hepatic dysfunctions induced by the parasite interfere with lipoprotein status. The decreased expression of exosomal miR122 represents an additional effect of Leishmania infection in dogs as in people.
Highlights
Leishmaniasis is a zoonosis caused by intracellular protozoa of the genus Leishmania transmitted by phlebotomines
The authors showed that, the glycoprotein gp63, present in Leishmania exosomes, was able to degrade Dicer1 in the hosts’ hepatic cells, reducing the synthesis of miR-122. Considering these premises, the aim of this study was twofold: evaluate the expression of serum exosomal miR-122 and the lipoprotein profile in dogs naturally infected by Leishmania infantum
The diagnosis of canine leishmaniasis (CL) was based on compatible clinical signs and confirmed by visualization of amastigotes in lymph nodal aspirates and serologically by a positive indirect fluorescent antibody test (IFAT) greater than 1:160 [22,23]
Summary
Leishmaniasis is a zoonosis caused by intracellular protozoa of the genus Leishmania transmitted by phlebotomines. A high tolerability of such cells to Leishmania spp. promotes a parasite survival in the canine liver leading to a perturbation of liver function and, in particular, cholesterol and lipoprotein metabolism [2,3]. Important differences between promastigotes and amastigotes of Leshmania chagasi have been observed regarding uptake through lipid rafts, subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids. A transient disruption of lipid rafts in cell membranes affected promastigote uptake, but not amastigote uptake by macrophages. These findings indicate a difference in the needs of Leishmania parasites regarding both the availability and origin of cholesterol. Leishmania protozoa can alter the metabolism of cholesterol directly or through the effect on lipoproteins; trypanosomatids are able to acquire cholesterol from low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs) by endocytosis [6,7,8]
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