High Content Analysis of Macrophage-Targeting
| Autor: | Nadine Kottmayr, Annika Bea, Hannelore Lotter, Chris Meier, Joachim Clos, Helena Fehling, Julie Sellau, Frederic Ting, Hanno Niss, Stefan Hoenow, Christine Brinker, Dirk Landschulze, Tim-Wolf Gilberger |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) 030231 tropical medicine Biology Microbiology Article Leishmania drug discovery 03 medical and health sciences Entamoeba histolytica 0302 clinical medicine Glycolipid In vivo Virology parasitic diseases medicine Parasite hosting Leishmania major lcsh:QH301-705.5 high content screening biology.organism_classification medicine.disease macrophages 030104 developmental biology Visceral leishmaniasis lcsh:Biology (General) High-content screening immunotherapy |
| Zdroj: | Microorganisms Volume 9 Issue 2 Microorganisms, Vol 9, Iss 422, p 422 (2021) |
| ISSN: | 2076-2607 |
| Popis: | An immunostimulatory glycolipid molecule from the intestinal protozoan parasite Entamoeba histolytica (Eh) and its synthetic analogs derived from its phosphatidylinositol-b-anchor (EhPIb) previously showed considerable immunotherapeutic effects against Leishmania major infection in vitro and in vivo. Here, we describe a high content screening assay, based on primary murine macrophages. Parasites detection is based on a 90 kDA heat shock protein-specific staining, enabling the detection of several Leishmania species. We validated the assay using L. major, L. braziliensis, L. donovani, and L. infantum as well as investigated the anti-leishmanial activity of six immunostimulatory EhPIb-compounds (Eh-1 to Eh-6). Macrophages infected with dermotropic species were more sensitive towards treatment with the compounds as their viability showed a stronger reduction compared to macrophages infected with viscerotropic species. Most compounds caused a significant reduction of the infection rates and the parasite burdens depending on the infecting species. Only compound Eh-6 was found to have activity against all Leishmania species. Considering the challenges in anti-leishmanial drug discovery, we developed a multi-species screening assay capable of utilizing non-recombinant parasite strains, and demonstrated its usefulness by screening macrophage-targeting EhPIb-compounds showing their potential for the treatment of cutaneous and visceral leishmaniasis. |
| Databáze: | OpenAIRE |
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