Baert, Lore Sarah, Mueller, Matthias, Doll, Thierry and Pellisson, Melanie (2024) iPS-derived human macrophages as an infection model for Leishmania donovani. PLoS neglected tropical diseases, 18. ISSN 1935-2735

Abstract

The parasite Leishmania donovani is one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40 000 lives each year. Despite its huge burden, the current drugs available all have severe drawbacks and there is an urgent need to find new antileishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifecycle of Leishmania. Here, we investigated the use of human induced pluripotent stem cell (iPS) derived macrophages (iMAC) as host cells for L. donovani. iMAC obtained through embryoid body differentiation were infected with L. donovani promastigotes and high content imaging techniques were used to optimize the iMAC seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50 values calculated for miltefosine and amphotericin B using the infected iMAC or mouse peritoneal macrophages as host cells in an assay are comparable to each other and to what has been reported in literature, showing its potential as a new drug screening assay.

Item Type:	Article
Date Deposited:	14 May 2024 00:45
Last Modified:	14 May 2024 00:45
URI:	https://oak.novartis.com/id/eprint/50914