Development of an ectopic huLiver model for Plasmodium liver stage infection.

Autor: Samayoa-Reyes G; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America., Flaherty SM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America., Wickham KS; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America., Viera-Morilla S; Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain., Strauch PM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America., Roth A; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America., Padrón L; Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain., Jackson CM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America., Meireles P; Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain., Calvo D; Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain., Roobsoong W; Faculty of Tropical Medicine, Mahidol Vivax Research Unit, Mahidol University, Bangkok, Thailand., Kangwanrangsan N; Faculty of Science, Pathobiology Department, Mahidol University, Bangkok, Thailand., Sattabongkot J; Faculty of Tropical Medicine, Mahidol Vivax Research Unit, Mahidol University, Bangkok, Thailand., Reichard G; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America., Lafuente-Monasterio MJ; Diseases of the Developing World, Infectious Diseases-Centre for Excellence in Drug Discovery (ID CEDD), GlaxoSmithKline, Tres Cantos, Madrid, Spain., Rochford R; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Mar 16; Vol. 18 (3), pp. e0279144. Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0279144
Abstrakt: Early Plasmodium falciparum and P. vivax infection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost in vivo model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against P. falciparum. Presented here is a new platform for the study of human Plasmodium infection with the potential to aid in drug discovery.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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