Plasma lipoproteins in visceral leishmaniasis and their effect onLeishmania-infected macrophages

Abstract

This work aimed at investigating the lipid profile of zoonotic visceral leishmaniasis (VL) patients' sera and the effect of lipoproteins on the in vitro production of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 and IL-12 by Leishmania infantum-infected and uninfected macrophages. Lipids were quantified in 26 VL patients' sera and 26 healthy controls from a VL endemic area. The patients' sera had higher triglyceride and very low density lipoprotein (VLDL) levels, and much lower apolipoprotein A1, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels than the control sera. Lipoprotein fractions were obtained by ultracentrifugation of sera. The addition of LDL and HDL to Leishmania-infected and uninfected macrophages, in physiological concentrations, enhanced the production of IL-6 and IL-10, but not of IL-12. LDL stimulated the production of TNF-alpha only in infected macrophages, whereas HDL stimulated the production of lower amounts of TNF-alpha in both infected and uninfected macrophages. VLDL stimulated only the production of IL-10. It is proposed herein that LDL may influence the development of VL by promoting the production of TNF-alpha by infected macrophages. A decrease in plasma LDL in some VL patients (to 20 mg/mL or less); however, would tend to reduce the production of TNF-alpha and therefore to limit the development of immune-mediated pathology, not withstanding the fact that it would perhaps increase the permissiveness of macrophages to Leishmania growth.

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs

“…The HDL levels (reference values >35mg/dl) and triglycerides levels (reference value <150mg/dL) were below and higher than normal in patients before treatment, respectively. These results are in agreement with Soares et al 25 , who showed that patients with VL had high triglycerides levels and low HDL, LDL and total cholesterol levels. Other studies of visceral leishmaniasis and other infectious diseases, such as HIV and schistosomiasis, have reported the same lipid changes 28,[51][52][53][54] .…”

“…Low cholesterol levels in humans decrease the number of circulating lymphocytes, thus increasing the chances of mortality 23,34 . The decrease in lipoproteins may affect the immune response and the pathogenesis of the disease, as lipoproteins are related to the production of TNF-α, IL-6 and IL-10 25 . In addition to being targets for the immunomodulatory activity of lipoproteins, macrophages express lipoprotein receptors and are the host cells of the Leishmania parasite 57 .…”

“…Lipoproteins have the ability to modulate the immune response. Low density lipoproteins, such as very low-density lipoprotein (VLDL) and LDL, can inhibit lymphocyte proliferation in vitro 32,33 , and another study in VL patients found that lipoproteins altered the immune response and the pathogenesis of the disease by modulating cytokine production 25 .…”

“…Some studies have reported differences in body mass index (BMI), glucose, triglycerides and lipoproteins in patients with active VL [22][23][24] . Studies performed on patients with VL showed high triglyceride levels and low high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol levels 25,26 . Additionally, VL patients showed reduced serum cholesterol concentrations as a function of their splenic parasite burden 23,27 .…”

Hypertriglyceridemia: a possible diagnostic marker of disease severity in visceral leishmaniasis

“…The mechanism controlling its production is poorly understood and its acquirement by tissues is dependent upon the activity of enzymes such as endothelial lipoprotein lipase, which may be impaired in patients with VL [33]. Another study on plasma lipoproteins and its effect on Leishmania infected macrophages in VL suggests that LDL influence the production of tumor necrosis factor (TNF-α), while VLDL stimulates only the production of interleukin-10 (IL-10) and perhaps increase the permissiveness of macrophage to leishmania growth [34].…”