Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani

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. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However,...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2024-01, Vol.18 (1), p.e0011559-e0011559
Main Authors: Baert, Lore, Rudy, Serena, Pellisson, Mélanie, Doll, Thierry, Rocchetti, Romina, Kaiser, Marcel, Mäser, Pascal, Müller, Matthias
Format: Article
Language:English
Subjects:
Amphotericin B
Analysis
Animals
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Dosage and administration
Drug development
Drug screening
Drug therapy
Drugs
Humans
Imaging techniques
Induced Pluripotent Stem Cells
Infections
Laboratory animals
Leishmania donovani
Leishmaniasis
Leishmaniasis, Visceral - parasitology
Macrophages
Macrophages - parasitology
Mice
Mice, Inbred BALB C
Miltefosine
Multiplicity of infection
Parasites
Parasitic diseases
Patient outcomes
Penicillin
Pluripotency
Promastigotes
Protozoa
Stem cells
Tropical diseases
Vector-borne diseases
Visceral leishmaniasis
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Summary: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. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle of Leishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells for L. donovani. iMACs obtained through embryoid body differentiation were infected with L. donovani promastigotes, and high-content imaging techniques were used to optimize the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50 values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0011559