Year: 2022
Type: preprint
Abstract: Plasmodium vivax is the most widespread human malaria parasite. The presence of extravascular reservoirs, the early circulation of infective stages (gametocytes), and relapsing infections arising from dormant liver stages render this parasite particularly difficult to control and eliminate. Experimental research is limited by the lack of a continuous culture in vitro system that fulfills the parasite needs, namely its tropism for immature CD71+ red blood cells (RBCs). Here, we report a humanized mice model, which upon engraftment of human hematopoietic progenitor and stem cells (HPSCs), exhibits efficient human erythropoiesis. Humanized HIS-HEry mice inoculated with cryopreserved P. vivax samples sustain long-lasting asexual parasite multiplication within CD71+ human RBCs and differentiation into mature gametocytes that can be efficiently transmitted to Anopheles mosquitoes, leading to formation salivary-gland sporozoites. Blood stages can be sequentially transferred to uninfected humanized mice by injection of fresh or frozen infected bone marrow cells, providing a unique murine model for the long-term maintenance of P. vivax isolates. This work offers a novel experimental platform to investigate the biology of RBC invasion and intraerythrocytic P. vivax development in vivo and evaluate new interventions against this elusive human parasite.
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Radboud Universiteit, Radboud Universitair Medisch Centrum, Institut National de la Transfusion Sanguine, Université de Paris, National Institutes of Health, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W4283208728