Sera from Visceral Leishmaniasis Patients Display Oxidative Activity and Affect the TNF- α Production by Macrophages In Vitro

Abstract

Mammalian protection against leishmanial infection depends on the development of an effective immune response. Zoonotic visceral leishmaniasis (ZVL) patients are usually unable to mount an effective immune response against the parasite and indeed appear to be severely immunosuppressed. This suppression has strong nonspecific and specific components mediated by serum factors and leishmanicidal activity of infected macrophages, respectively. The lipid profile has been shown to be altered in ZVL patients' sera. This work aimed at (i) determining the HDL, Apo A1, LDL, and VLDL concentrations in ZVL patients' sera; (ii) investigating the oxidative effect of ZVL patients' sera on the β-carotene matrix; (iii) measuring IL-10, IL-6, IL-12p40, and tumour necrosis factor-α (TNF-α) concentrations in the macrophage cultures, to which 10% of ZVL patients' serum had been added. Levels of HDL, LDL fraction, and apolipoprotein A1 in ZVL patients' sera were lower than those of healthy individuals' sera, except for the mean level of VLDL. The matrix of β-carotene and linoleic acid system was oxidized in the presence of ZLV patients' sera. The presence of ZVL patients' sera did not modify the cytokine production of IL-6, IL-12p40, and IL-10 by human macrophages in vitro but TNF-α production was altered, probably due to lack of macrophage stimulation by lipoprotein.

Figure 1

Culture supernatants of PBMC-derived macrophages of healthy individuals were collected 24 hours after the addition of 10% of zoonotic visceral leishmaniasis (ZVL) or healthy individuals' serum to measure cytokine concentrations by ELISA. The data represent the mean of three experiments with cells from different donors. All cultures were done in the presence of 10% normal AB serum. ^★p < 0.05; unpaired Student's t-test.