Altered composition and functional profile of high-density lipoprotein in leprosy patients

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 This accumulation in host peripheral tissues should be withdrawn by HDL, but it is unclear why this lipoprotein from Mb patients loses this function.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 HDLcholesterol 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.

Household Contacts of Leprosy Patients in Endemic Areas Display a Specific Innate Immunity Profile

“…The role and functionality of ApoA1 in leprosy thus remains to be further elucidated. The influence of ApoA1 on lipid metabolism is of interest as dysfunctional high-density lipoprotein (involved in cholesterol transport to the liver of which the main protein is ApoA1) related to altered ApoA1 levels has been observed in MB patients ( 34 ). Moreover, it was suggested that M. leprae can directly affect ApoA1 biosynthesis.…”

Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

“…HDL has been found to contain a diverse set of enzymatically active proteins, hydroxylated derivatives of polyunsaturated fatty acids, and hydroperoxides, and although HDL is regarded as anti-oxidative and antiinflammatory, during the acute phase reaction, oxidative and inflammatory reactions take over (Lemes et al, 2020;Navab et al, 2001;Vaisar et al, 2007). Our finding that PLY-modified HDL contains a high concentration of MDA suggests dysfunction of the particle and enhancement of oxidative reactions (Shao et al, 2010).…”

The Role of Lipid and the Benefit of Statin in Augmenting Rifampicin Effectivity for a Better Leprosy Treatment

“…The result of the studies has been sum up in Table 1. Among the 15 studies, we summarize that the main topics discussed related to lipid and leprosy include: (1) Serum lipid profile alterations in leprosy in six studies [20], [21], [22], [25], [27], [28] (2); lipid metabolism in leprosy and role of their metabolites [23], [24], [32];…”