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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ftdoajarticles:oai:doaj.org/article:0559f775e19b434eb173945480fa2e87 2024-02-11T10:01:20+01:00 Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. Lore Baert Serena Rudy Mélanie Pellisson Thierry Doll Romina Rocchetti Marcel Kaiser Pascal Mäser Matthias Müller 2024-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011559 https://doaj.org/article/0559f775e19b434eb173945480fa2e87 EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011559&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011559 https://doaj.org/article/0559f775e19b434eb173945480fa2e87 PLoS Neglected Tropical Diseases, Vol 18, Iss 1, p e0011559 (2024) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2024 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011559 2024-01-21T01:39:16Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 18 1 e0011559 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Lore Baert Serena Rudy Mélanie Pellisson Thierry Doll Romina Rocchetti Marcel Kaiser Pascal Mäser Matthias Müller Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Lore Baert Serena Rudy Mélanie Pellisson Thierry Doll Romina Rocchetti Marcel Kaiser Pascal Mäser Matthias Müller |
author_facet |
Lore Baert Serena Rudy Mélanie Pellisson Thierry Doll Romina Rocchetti Marcel Kaiser Pascal Mäser Matthias Müller |
author_sort |
Lore Baert |
title |
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
title_short |
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
title_full |
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
title_fullStr |
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
title_full_unstemmed |
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani. |
title_sort |
induced pluripotent stem cell-derived human macrophages as an infection model for leishmania donovani. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2024 |
url |
https://doi.org/10.1371/journal.pntd.0011559 https://doaj.org/article/0559f775e19b434eb173945480fa2e87 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 18, Iss 1, p e0011559 (2024) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011559&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011559 https://doaj.org/article/0559f775e19b434eb173945480fa2e87 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011559 |
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PLOS Neglected Tropical Diseases |
container_volume |
18 |
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1 |
container_start_page |
e0011559 |
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