Journal
MICROORGANISMS
Volume 9, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms9020422
Keywords
Leishmania; immunotherapy; high content screening; macrophages; drug discovery
Categories
Funding
- Joachim Herz Graduate School of Infection Biology at the Bernhard Nocht Institute for Tropical Medicine, Hamburg
- DZIF (German Center for Infection Research) Academy, Braunschweig [TI 07.003-FP2016]
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A study introduced an immunostimulatory glycolipid molecule from the intestinal protozoan parasite Entamoeba histolytica (Eh) and its synthetic analogs for potential immunotherapeutic effects against Leishmania major infection. Using a screening assay based on primary murine macrophages, the research demonstrated the potential of six immunostimulatory EhPIb-compounds for treating cutaneous and visceral leishmaniasis, with compound Eh-6 exhibiting activity against all Leishmania species.
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.
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