Plasmodium falciparum-infected humanized mice: a viable preclinical tool
1Division of Cell Biology & Immunology, Biomedical Parasitology & Nano-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh, 160036, India.
Abstract:
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 , 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.
Insights
Mouse-human chimeras offer insights into infectious diseases like malaria. Humanized immunodeficient mice are crucial for studying Plasmodium falciparum due to limitations in in vitro models and drug resistance challenges.
Area of Science:
- Infectious Diseases
- Immunology
- Parasitology
- Chimeric Mice Models
Background:
- In vitro culture of Plasmodium falciparum is insufficient for understanding its complex biology, drug resistance, and pathogenesis.
- Challenges in malaria research include the parasite's complex life cycle, genome, drug resistance evolution, and diagnostic limitations.
- The lack of effective vaccines and increasing drug resistance necessitate advanced research models.
Purpose of the Study:
- To highlight the utility of humanized immunodeficient mouse models for studying Plasmodium falciparum.
- To explore the application of chimeric mice in understanding infectious diseases, particularly malaria.
- To discuss the role of human cell/tissue reconstituted mice in overcoming limitations of in vitro studies.
Main Methods:
- Utilizing various immunodeficient mouse strains (e.g., TK/NOG, FRG/NOD, NOD/SCID/IL-2 receptor γ chain, NSG, NRG) for humanization.
- Employing CD34+ human hematopoietic stem cell-engrafted NSG mice to reconstitute the human immune system.
- Challenging these humanized mice with Plasmodium falciparum to study infection dynamics.
Main Results:
- Humanized immunodeficient mice support the engraftment and study of Plasmodium falciparum infection.
- These models facilitate research into parasitology, pharmacology, and immunology related to malaria.
- Human immune system (CD34+ HSC-NSG) mice enable the study of immune effectors in systemic inflammatory diseases.
Conclusions:
- Humanized immunodeficient mice are essential tools for advancing malaria research and understanding Plasmodium falciparum.
- These models provide a more comprehensive platform than in vitro cultures for drug discovery and vaccine development.
- Chimeric mouse models are critical for dissecting host-pathogen interactions and developing strategies against infectious diseases.
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