Modelling amoebic brain infection caused by Balamuthia mandrillaris using a human cerebral organoid.

Autor: Tongkrajang N; Siriraj Integrative Center for Neglected Parasitic Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Kobpornchai P; Siriraj Integrative Center for Neglected Parasitic Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Siriraj-Long Read Lab, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Dubey P; Siriraj Integrative Center for Neglected Parasitic Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Chaisri U; Department of Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Kulkeaw K; Siriraj Integrative Center for Neglected Parasitic Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Siriraj-Long Read Lab, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Jun 20; Vol. 18 (6), pp. e0012274. Date of Electronic Publication: 2024 Jun 20 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012274
Abstrakt: The lack of disease models adequately resembling human tissue has hindered our understanding of amoebic brain infection. Three-dimensional structured organoids provide a microenvironment similar to human tissue. This study demonstrates the use of cerebral organoids to model a rare brain infection caused by the highly lethal amoeba Balamuthia mandrillaris. Cerebral organoids were generated from human pluripotent stem cells and infected with clinically isolated B. mandrillaris trophozoites. Histological examination showed amoebic invasion and neuron damage following coculture with the trophozoites. The transcript profile suggested an alteration in neuron growth and a proinflammatory response. The release of intracellular proteins specific to neuronal bodies and astrocytes was detected at higher levels postinfection. The amoebicidal effect of the repurposed drug nitroxoline was examined using the human cerebral organoids. Overall, the use of human cerebral organoids was important for understanding the mechanism of amoeba pathogenicity, identify biomarkers for brain injury, and in the testing of a potential amoebicidal drug in a context similar to the human brain.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Tongkrajang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje