Plasmodium falciparum-infected humanized mice: a viable preclinical tool

Abstract

Summary Extensive research conducted on mouse–human chimeras has advanced our understanding on infectious diseases including the human–malaria parasite, Plasmodium falciparum. In vitro culture of asexual-blood stage infection of P. falciparum does not answer all questions related to parasitology, pharmacology and immunology, and complex life cycle, complicated genome, evolution of drug resistance and poor diagnosis makes it difficult to understand the patho-biology of parasite. Unavailability of effective-vaccine and issues of drug resistance advocates the use of human cell/tissues reconstituted immunodeficient-mice to P. falciparum. A number of immunodeficient-strains (TK/NOG, FRG/NOD, NOD/SCID/IL-2 receptor γ chain  null, NOD severe combined immunodeficiency gamma [NSG] mouse and NOD.Rag1−/− IL2Rγ−/−  [NRG; DRAG]) are used for humanization purposes. Additionally, human-hematopoietic stem cells (CD34 reconstituted-NSG [human immune system]) mice support the engraftment and repopulation of immune effecters to study systemic inflammatory diseases.