Abstract
The changes in host lipid metabolism during leprosy have been correlated to fatty acid alterations in serum and with high-density lipoprotein (HDL) dysfunctionality. This is most evident in multibacillary leprosy patients (Mb), who present an accumulation of host lipids in Schwann cells and macrophages. This accumulation in host peripheral tissues should be withdrawn by HDL, but it is unclear why this lipoprotein from Mb patients loses this function. To investigate HDL metabolism changes during the course of leprosy, HDL composition and functionality of Mb, Pb patients (paucibacillary) pre- or post-multidrug therapy (MDT) and HC (healthy controls) were analyzed. Mb pre-MDT patients presented lower levels of HDL-cholesterol compared to HC. Moreover, Ultra Performance Liquid Chromatography-Mass Spectrometry lipidomics of HDL showed an altered lipid profile of Mb pre-MDT compared to HC and Pb patients. In functional tests, HDL from Mb pre-MDT patients showed impaired anti-inflammatory and anti-oxidative stress activities and a lower cholesterol acceptor capacity compared to other groups. Mb pre-MDT showed lower concentrations of ApoA-I (apolipoprotein A-I), the major HDL protein, when compared to HC, with a post-MDT recovery. Changes in ApoA-I expression could also be observed in M. leprae-infected hepatic cells. The presence of bacilli in the liver of a Mb patient, along with cell damage, indicated hepatic involvement during leprosy, which may reflect on ApoA-I expression. Together, altered compositional and functional profiles observed on HDL of Mb patients can explain metabolic and physiological changes observed in Mb leprosy, contributing to a better understanding of its pathogenesis.
Highlights
Leprosy is a human disease characterized by a spectrum of clinical manifestations that occurs due to a wide range of immune responses against Mycobacterium leprae, the causative agent of the disease
It was observed that highdensity lipoprotein (HDL) has an altered lipid composition in Mb patients before multidrug therapy (MDT), which may lead to an impairment of its functions
Our group showed in nerve biopsies of Mb patients and in vitro cultures infected with M. leprae that, besides macrophages, Schwann cells displayed a great number of lipid droplets [6, 7]
Summary
Leprosy is a human disease characterized by a spectrum of clinical manifestations that occurs due to a wide range of immune responses against Mycobacterium leprae, the causative agent of the disease. Previous works from our group demonstrated that Virchow cells found in dermal lesions of Mb patients are highly positive for adipose differentiation-related protein (ADRP), a classical marker for the cellular organelles called lipid droplets [6]. Cruz et al [9] findings indicated that highdensity lipoprotein (HDL) from Mb patients is not functional This possibly favors the accumulation of oxidized phospholipids in Virchow cells, since the main HDL function is the reverse transport of cholesterol, phospholipids and non-esterified fatty acids from peripheral tissues to the liver [14,15,16], being able to reverse the formation of foam cells and reducing the volume of atherosclerotic plaques [17]. It is unclear why HDL from Mb patients loses its function
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