4.2 Article

Plasmodium falciparum infected humanized mice: a viable preclinical tool

Journal

IMMUNOTHERAPY
Volume 13, Issue 16, Pages -

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/imt-2021-0102

Keywords

CD34; cellular and humoral immunity; FRG; HSC; immune response; knock-out; NSG; NSG mice; P; falciparum; PfhuHep-TK-NOG; vaccine

Categories

Funding

  1. Department of Science and Technology (DST), Govt of India [ECR/2015/000264]
  2. DBT, New Delhi, India in Ramalingaswami Re-entry Fellowship Project [BT/RLF/Re-entry/27/2018]

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Extensive research on mouse-human chimeras has contributed to our understanding of infectious diseases, especially in the case of the human-malaria parasite Plasmodium falciparum. The complex life cycle and genome of P. falciparum, along with drug resistance issues, pose challenges for parasitology research. Utilizing human cell/tissue reconstituted immunodeficient mice is a promising approach for studying these aspects and addressing the lack of effective vaccine and drug resistance concerns.
Extensive research conducted on mouse-human chimeras has advanced our understanding on infectious diseases including the human-malaria parasite, Plasmodium falciparum (P. 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 gamma chain (null), NOD severe combined immunodeficiency gamma [NSG] mouse, NOD.Rag1-/- IL2R gamma-/- [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.

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