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http://hdl.handle.net/2445/103907
Title: | A humanized mouse model for sequestration of Plasmodium falciparum sexual stages and in vivo evaluation of gametocytidal drugs |
Author: | Duffier, Yoann Lorthiois, Audrey Cisteró, Pau Dupuy, Florian Jouvion, Gregory Fiette, Laurence Mazier, Dominique Mayor Aparicio, Alfredo Gabriel Lavazec, Catherine Moreno Sabater, Alicia |
Keywords: | Malària Plasmodium falciparum Malaria Plasmodium falciparum |
Issue Date: | 12-Oct-2016 |
Publisher: | Springer Nature |
Abstract: | The development of new drugs to disrupt malaria transmission requires the establishment of an in vivo model to address the biology of Plasmodium falciparum sexual stages (gametocytes). Herein we show that chemically immune-modulated NSG mice grafted with human erythrocytes support complete sexual development of P. falciparum parasites and generate high gametocytemia. Immunohistochemistry and RT-qPCR analyses indicate an enrichment of immature gametocytes in the bone marrow and the spleen, suggesting a sequestration mechanism reminiscent to that observed in humans. Upon primaquine treatment, elimination of gametocytes from peripheral blood and from sequestration sites was observed, providing a proof of concept that these mice can be used for testing drugs. Therefore, this model allows the investigation of P. falciparum sexual commitment, gametocyte interactions with the bone marrow and spleen and provides the missing link between current in vitro assays and Phase I trials in humans for testing new malaria gametocytidal drugs. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1038/srep35025 |
It is part of: | Scientific Reports, 2016, vol. 6, p. 35025 |
URI: | http://hdl.handle.net/2445/103907 |
Related resource: | http://dx.doi.org/10.1038/srep35025 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (ISGlobal) |
Files in This Item:
File | Description | Size | Format | |
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duffier2016_2274.pdf | 1.55 MB | Adobe PDF | View/Open |
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