Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells

Abstract

Apparently for the first time, the peripheral blood monocytes of individuals with active visceral leishmaniasis (VL) have been found to show reduced expression of interferon gamma receptor-1 (IFNGR1). Since interferon gamma is the main cytokine responsible for defence against leishmanial parasites, it was thought possible that effective antileishmanial drugs may up-regulate IFNGR1. Confocal microscopy confirmed that monocytes from VL patients who had been treated, with sodium antimony gluconate (SAG), did display IFNGR1 up-regulation. To see if this effect could be mimicked in vitro, IFNGR1 expression was investigated using a human macrophage cell line (THP1), northern blotting and confocal microscopy. When the THP1 cells were treated with SAG or pentamidine, their expression of the receptor was increased. This drug-induced up-regulation was more intense if the macrophages were infected with Leishmania donovani than if they were left uninfected. The possibility that at least some antileishmanial drugs act by up-regulating IFNGR1 expression needs to be explored further. A good model for investigating the mechanisms of action of antileishmanial drugs might be based on the THP1 cell line.