TITLE

A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes

AUTHOR(S)
Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Mulet, Teresa; Rullas, Joaquín; Herreros, Esperanza; Ferrer, Santiago; Jiménez, Elena; Mendoza, Alfonso; Regadera, Javier; Rosenthal, Philip J.; Bathurst, Ian; Pompliano, David L.; de las Heras, Federico Gómez; Gargallo-Viola, Domingo
PUB. DATE
May 2008
SOURCE
PLoS ONE;2008, Vol. 3 Issue 5, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NODscid/b2m-/- mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NODscid/b2m-/- mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D70087/N9 as a reference strain for model development. Pf3D70087/N9 caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.
ACCESSION #
55425732

 

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