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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
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.
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It is part of: Scientific Reports, 2016, vol. 6, p. 35025
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (ISGlobal)

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