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Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes

A major constraint in the study of Plasmodium falciparum malaria, including vaccine development, lies on the parasite's strict human host specificity and therefore the shortage of animal experimental models able to harbor human plasmodia. The best experimental models are neo-tropical primates o...

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Autores principales: Cunha, Janaiara A., Carvalho, Leonardo J. M., Bianco-Junior, Cesare, Andrade, Márcia C. R., Pratt-Riccio, Lilian R., Riccio, Evelyn K. P., Pelajo-Machado, Marcelo, da Silva, Igor J., Druilhe, Pierre, Daniel-Ribeiro, Cláudio Tadeu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613086/
https://www.ncbi.nlm.nih.gov/pubmed/28983468
http://dx.doi.org/10.3389/fcimb.2017.00408
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author Cunha, Janaiara A.
Carvalho, Leonardo J. M.
Bianco-Junior, Cesare
Andrade, Márcia C. R.
Pratt-Riccio, Lilian R.
Riccio, Evelyn K. P.
Pelajo-Machado, Marcelo
da Silva, Igor J.
Druilhe, Pierre
Daniel-Ribeiro, Cláudio Tadeu
author_facet Cunha, Janaiara A.
Carvalho, Leonardo J. M.
Bianco-Junior, Cesare
Andrade, Márcia C. R.
Pratt-Riccio, Lilian R.
Riccio, Evelyn K. P.
Pelajo-Machado, Marcelo
da Silva, Igor J.
Druilhe, Pierre
Daniel-Ribeiro, Cláudio Tadeu
author_sort Cunha, Janaiara A.
collection PubMed
description A major constraint in the study of Plasmodium falciparum malaria, including vaccine development, lies on the parasite's strict human host specificity and therefore the shortage of animal experimental models able to harbor human plasmodia. The best experimental models are neo-tropical primates of the genus Saimiri and Aotus, but they require splenectomy to reduce innate defenses for achieving high and consistent parasitemias, an important limitation. Clodronate-liposomes (CL) have been successfully used to deplete monocytes/macrophages in several experimental models. We investigated whether a reduction in the numbers of phagocytic cells by CL would improve the development of P. falciparum parasitemia in non-splenectomized Saimiri sciureus monkeys. Depletion of S. sciureus splenocytes after in vitro incubation with CL was quantified using anti-CD14 antibodies and flow cytometry. Non-infected and P. falciparum-infected S. sciureus were injected intravenously twice a week with either CL at either 0.5 or 1 mL (5 mg/mL) or phosphate buffered saline (PBS). Animals were monitored during infection and treated with mefloquine. After treatment and euthanasia, spleen and liver were collected for histological analysis. In vitro CL depleted S. sciureus splenic monocyte/macrophage population in a dose- and time-dependent manner. In vivo, half of P. falciparum-infected S. sciureus treated with CL 0.5 mL, and two-thirds of those treated with CL 1 mL developed high parasitemias requiring mefloquine treatment, whereas all control animals were able to self-control parasitemia without the need for antimalarial treatment. CL-treated infected S. sciureus showed a marked decrease in the degree of splenomegaly despite higher parasitemias, compared to PBS-treated animals. Histological evidence of partial monocyte/macrophage depletion, decreased hemozoin phagocytosis and decreased iron recycling was observed in both the spleen and liver of CL-treated infected S. sciureus. CL is capable of promoting higher parasitemia in P. falciparum-infected S. sciureus, associated with evidence of partial macrophage depletion in the spleen and liver. Macrophage depletion by CL is therefore a practical and viable alternative to surgical splenectomy in this experimental model.
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spelling pubmed-56130862017-10-05 Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes Cunha, Janaiara A. Carvalho, Leonardo J. M. Bianco-Junior, Cesare Andrade, Márcia C. R. Pratt-Riccio, Lilian R. Riccio, Evelyn K. P. Pelajo-Machado, Marcelo da Silva, Igor J. Druilhe, Pierre Daniel-Ribeiro, Cláudio Tadeu Front Cell Infect Microbiol Microbiology A major constraint in the study of Plasmodium falciparum malaria, including vaccine development, lies on the parasite's strict human host specificity and therefore the shortage of animal experimental models able to harbor human plasmodia. The best experimental models are neo-tropical primates of the genus Saimiri and Aotus, but they require splenectomy to reduce innate defenses for achieving high and consistent parasitemias, an important limitation. Clodronate-liposomes (CL) have been successfully used to deplete monocytes/macrophages in several experimental models. We investigated whether a reduction in the numbers of phagocytic cells by CL would improve the development of P. falciparum parasitemia in non-splenectomized Saimiri sciureus monkeys. Depletion of S. sciureus splenocytes after in vitro incubation with CL was quantified using anti-CD14 antibodies and flow cytometry. Non-infected and P. falciparum-infected S. sciureus were injected intravenously twice a week with either CL at either 0.5 or 1 mL (5 mg/mL) or phosphate buffered saline (PBS). Animals were monitored during infection and treated with mefloquine. After treatment and euthanasia, spleen and liver were collected for histological analysis. In vitro CL depleted S. sciureus splenic monocyte/macrophage population in a dose- and time-dependent manner. In vivo, half of P. falciparum-infected S. sciureus treated with CL 0.5 mL, and two-thirds of those treated with CL 1 mL developed high parasitemias requiring mefloquine treatment, whereas all control animals were able to self-control parasitemia without the need for antimalarial treatment. CL-treated infected S. sciureus showed a marked decrease in the degree of splenomegaly despite higher parasitemias, compared to PBS-treated animals. Histological evidence of partial monocyte/macrophage depletion, decreased hemozoin phagocytosis and decreased iron recycling was observed in both the spleen and liver of CL-treated infected S. sciureus. CL is capable of promoting higher parasitemia in P. falciparum-infected S. sciureus, associated with evidence of partial macrophage depletion in the spleen and liver. Macrophage depletion by CL is therefore a practical and viable alternative to surgical splenectomy in this experimental model. Frontiers Media S.A. 2017-09-21 /pmc/articles/PMC5613086/ /pubmed/28983468 http://dx.doi.org/10.3389/fcimb.2017.00408 Text en Copyright © 2017 Cunha, Carvalho, Bianco-Junior, Andrade, Pratt-Riccio, Riccio, Pelajo-Machado, da Silva, Druilhe and Daniel-Ribeiro. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Cunha, Janaiara A.
Carvalho, Leonardo J. M.
Bianco-Junior, Cesare
Andrade, Márcia C. R.
Pratt-Riccio, Lilian R.
Riccio, Evelyn K. P.
Pelajo-Machado, Marcelo
da Silva, Igor J.
Druilhe, Pierre
Daniel-Ribeiro, Cláudio Tadeu
Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title_full Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title_fullStr Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title_full_unstemmed Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title_short Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes
title_sort increased plasmodium falciparum parasitemia in non-splenectomized saimiri sciureus monkeys treated with clodronate liposomes
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613086/
https://www.ncbi.nlm.nih.gov/pubmed/28983468
http://dx.doi.org/10.3389/fcimb.2017.00408
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