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Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Infectivity of five different types of macrophages by Leishmania infantum
1Unidade de Leishmanioses, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, R. da Junqueira, 96, 1349-008 Lisboa, Portugal.
Abstract:
Leishmania are intracellular parasites that multiply as the amastigote form in the macrophages of their vertebrate hosts. Since vaccines against leishmaniases are still under development, the control of these diseases relies on prompt diagnosis and chemotherapy in infected humans as well as in dogs, which are the main reservoir of Leishmania infantum, in Mediterranean countries. To establish the macrophage type to be used as an in vitro model for antileishmanial chemotherapeutic studies, we analysed the susceptibility of human peripheral blood derived macrophages, macrophages derived from mouse bone marrow, mouse peritoneal macrophages and macrophages differentiated from cell lines U-937 and DH82 to infection by two L. infantum strains, one obtained from a human leishmanial infection and other from a canine infection. Both strains displayed comparable behaviour in their capacity of infecting the different macrophage types. Human peripheral blood macrophages and DH82 cells were less infectable by both strains. U-937, mouse peritoneal macrophages and mouse bone marrow derived macrophages are the most active cells to phagocytose the parasites. However, U-937 cell line appears to be the most useful as Leishmania infection model providing an unlimited source of homogeneous host cells with reproducibility of the results, is less time consuming, less expensive and tolerate high doses of first line drugs for human and canine visceral leishmaniasis treatment.
Insights
The U-937 cell line is the best in vitro model for studying Leishmania infantum infections. It offers a reproducible, cost-effective, and time-efficient method for antileishmanial drug development in humans and dogs.
Area of Science:
- Parasitology
- Immunology
- Drug Discovery
Background:
- Leishmania parasites infect macrophages, causing leishmaniasis.
- Vaccines are unavailable, making chemotherapy essential for disease control.
- Dogs are a significant reservoir for Leishmania infantum in Mediterranean regions.
Purpose of the Study:
- To identify the optimal macrophage model for in vitro antileishmanial drug screening.
- To compare the infectivity of Leishmania infantum in various macrophage types.
Main Methods:
- Infection of human peripheral blood-derived macrophages, mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and U-937 and DH82 cell lines with L. infantum.
- Assessment of parasite infectivity across different macrophage models.
Main Results:
- Human peripheral blood macrophages and DH82 cells showed lower susceptibility to L. infantum infection.
- U-937 cells, mouse peritoneal macrophages, and mouse bone marrow-derived macrophages were highly phagocytic.
- U-937 cells demonstrated superior utility as a Leishmania infection model due to homogeneity, reproducibility, cost-effectiveness, and drug tolerance.
Conclusions:
- The U-937 cell line is a highly suitable and practical in vitro model for Leishmania infection studies.
- This model facilitates reproducible and efficient research into new treatments for human and canine leishmaniasis.
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